That's not a problem, coming up with plot threads/hooks/villains. The problem is figuring out the structure - much of the campaign has been some variety of hack-n-slash.
But if you think it will help, here's a summary.
They encounter a thief, who returns several times.
A Mercykiller troll assassinates a Hardhead tiefling whose eyes glow with ethereal light. A tiefling thief, Hrundlefrost, finds out and animates the victim's eyes for personal use. The party chases away Hrundlefrost and keeps the eyes, before going on to beat up the troll and toss his unconscious remains through a one-way portal to the Abyss.
Hrundlefrost stalks the party, attempting to snatch the animated eyes, but is spotted and chased away several times. After the third attempt, Naught catches him, cuts off his head, and tosses both into a furnace. Hrundlefrost's brother, a Tome Assassin known as Black Spot, gets him reincarnated; then approaches the party to tell them they owe him for killing Hrundlefrost [cost of reincarnation + restoration]gp without explaining his relation. They tell him to pound sand, he one shots the wizard PC (all subdual damage) and disappears from sight, and uses ventriloquism to tell the party he'll be back later for the first half of what they owe him.
They explore Dis, several prime worlds, encounter several different spelljamming races, and encounter a prison in Elysium with artifacts of ancient power.
They are hired by Natalia von Chasm to explore a piece of territory several days' walk outside of the City of Dis. Not a whole lot happens here, but it establishes a business relationship with Natalia.
They get a job from a Sigilian tavern. A messenger is going to be executed in two days if he doesn't personally deliver a message to Othar, the Earl of Bladereach, who has gone missing. The party eventually find him, rescue him from spelljamming grioth that had crashed nearby, and get paid well.
Natalia hires them again to test out a new alchemical reagent that protects the user from Elysium's entrapping quality. There's some random corporate espionage, Hades hazards, etc.
A level 15 Tome Marshal had an accident and was stranded in Elysium and rolled a natural 1 in his first week while trying to get rescued. This is really bad, as he was vital in saving the world of Bustlum (one of the PC's homeworld) from an invasion of scro. Thanks to their new concoction of protection, they delve into the third layer of Elysium, knock out the Marshal, and drag him to Sigil. While they were there, they found an ancient dungeon with four magic items in them, and all of the traps were too old to pose a threat to them. While the Marshal (who gets cured of the entrapment since he's outside of Elysium) does his thing, the party fights some scro and helps evacuate a number of gnomes.
They explore a buttload of prime worlds for a base, essentially none are good enough.
It's at this point the party decides they want to have their own base on a Prime. A few adventures are had as they explore world after world, seeking a suitable place. One prime, ruled by unusually powerful/decadent mephits, captures them and forces them to gladiatorial combat; but they eventually escape. Another prime is eerily empty of ALL animal life (no squirrels in the forest, no fish in the sea, nothing), but because it was monsoon season when they went, they assumed it was hurricanes year-round; that realm also gave them a very potent fungal infection in their minds that took nearly a month for symptoms to manifest (as well as cure disease & remove curse to treat). There were several other portals to various primes that were deemed unsuitable for building a base; too many of the plants were poisonous, the abandoned city had too many secret doors, the locals could see through walls, not enough trees/stone for construction, etc.
They deal with the brother of the thief from the beginning, who bothers them at several points (though not a single PC remains that’s directly interacted with the assassin now)
After getting threatened by Black Spot for the first payment, they are ambushed who they think is him (an orc in his pajamas) and kill him dead (wife's across the street, but keeps quiet). When Black Spot sends another message after this event, they give the first payment so they can avoid being distracted and go on a plot hook to raid a nobleman's house; a dark creeper beggar offered them a portal key and directions to an unseelie fey noble's house in the Plane of Shadow, said noble having seemingly abandoned their estate at least a decade ago. They take the portal and ransack the place, even acquiring a calligraphy dragon named Arthur, learning that the original inhabitant likely died in a war on behalf of the Uradel (a kind of Shadow plane fey nobility). They also acquire a really encrypted notebook, which takes a fair bit of magic and hiring experts to decipher; it's a map to a dungeon! It's also a spellbook holding several of Tasha's spells (including Tomb Tesselation).
They are served papers by the Harmonium, on trial for the murder of an orc carpenter (whom they thought was Black Spot). His wife has an exceptionally well-paid barrister, and they see clear evidence of the judge getting bribed. Briefly contemplating killing the orc woman, they decide to hire a lawyer from the Celestial Bureaucracy, owing a favour in return. They get out of the murder charge on self-defense, and do the favour, go to Arcadia and convince one of the mountains to stop being on strike and let gravity operate (this involves beating him up, mythological style).
They mess around with temporal shenanigans, an earlier exploration on the Prime getting caught in the mess.
Remember Othar, the Earl of Bladereach, from level 3? He's forgotten by everyone except the party, and they find themselves randomly finding themselves in the middle of a fight scene of what seems like an alternate timeline before reverting back to normal. Using the adventure from Bruce Cordell's If Thoughts Could Kill, with kit-bashing to incorporate temporal shenanigans & a rogue axiomite as an expy of The Doctor.
They settle a home base on a tropical island that other adventurers appreciate as well.
They finally find a Prime world they like. A tropical island that two other adventuring groups also have built homes. Two of the players have Leadership, and send their followers to start building a house into the side of the dead volcano, and hang out with the locals and the other adventurers on the island. It's at this point they're approached again by Black Spot, who demands the final payment. As the money is trivial, they agree to drop off the "payment" at a certain drop point; which they do so...in very bulky trade goods (a large wheelbarrow full of artisanal socks, copper pipes, etc). They try to secretly follow the cyclops that arrives to pick up the payment, figuring it to be Black Spot's agent; but even after having their followers take turns watching the cyclop's home, they find no indication who Black Spot might be.
They travel to weird realms, learning that their artifacts of ancient power are waay more dangerous than they realized
They suit up and begin to go to the dungeon spoken of in that notebook from the Uradel's house, requiring use of Tasha's Tomb Transport to reach the entrance. The dungeon itself is a physically manifested dream of a kaiju (200' tall, four armed humanoid adamantine-like golem, destroys air in its presence), the entrance directly in front of its head. They get inside, explore the labyrinth, and find the treasure - the second part of those four magic items they got from Elysium. The items upgrade in potency, become clearly evil, and are now permanently attached to each PC. They do some preliminary research, finding out that these artifacts are the remnant bodies of the Four Demon Brothers, a set of four entities so powerful and evil that in the primordial era, they were sundered into three parts (mind, body, soul) and stored in far corners of the multiverse; their names and memory stricken from the Akashic Record. Them breaking them out and wearing them has begun the process of ancient forces starting to remember. If their third component(s) are reunited, they will be complete and able to operate independently. Because thinking about them writes them into the Akashic Record, the players opt to ignore this and wait until they're higher level to deal with the problem, enjoying the benefits of more powerful magic items until then.
They explore the Astral for wealth.
Wanting Wish-economy wealth, they do some rumour delving for possible leads on Astral Diamonds. They go to the astral, travel a bit, run into a civilized (doesn't mean they're nice) roper, and carve out some diamonds before the githyanki arrive.
They travel the Prime to fight a genocidal archdruid, twice, and even encounter that assassin from earlier again
The oracle’s followers, who is from the same homeworld, reports that the portal they use to visit their home Prime is no longer functioning. They travel there, discovering that the continent is being slaughtered. An Archdruid has made a pact with the fey (seelie and uradel, specifically) and is throwing the full fury of nature in what is virtually a one-man army against civilization (that nobody in the setting besides him is above level ten really, really helps). He's personally casting spells that bury an entire city beneath twenty four feet of snow in two minutes. They fight an awakened hawk sorcerer, several fey of the Wild Hunt, etc. Eventually, they reach the Archdruid and kill him.
It's at this point, they decide they don't like Black Spot, and go back to searching for him. They find out a local Sigilian noble is obsessed with the assassin, as he had killed his entire family a year ago and mocked him several times. Several rumours persisted that this nobleman was targeted by a rival that had hired Black Spot to mess with him, and it seemed to be working; as the noble's been acting mad and bleeding his funds try in obsession with catching Black Spot. Comparing notes, they find out Black Spot is currently operating in a town in the Outlands. When they arrive, an evil treant noble (later, they find out his name is Black Spot) screams in rage at the sight of the party and attacks ruthlessly. After self-defending the treant to ashes, they find out it was all a ruse. Returning to Sigil, they find out that the nobleman was killed by the assassin several weeks ago and led the party on a wild goose chase.
Taking a bit of a break, they do several various favours with merchants in Sigil that deal in Wish-economy wealth; including A'kin the Friendly Fiend, Zedara the Titan of Wealth, & Estavan the Ogre Mage of the Planar Trade Consortium. During this time frame, Twilight Oblivion joins the party, agreeing to help with a lead on more wealth if they afterward help her get revenge on whomever killed her clan. On the side quest (of which there were several time sensitive options), they choose the one where one of the gods of the night had an accident and spilled the contents of their crafts box somewhere in the Beastlands; as the contents include a moon and several stars (aka, several litres of Liquid Hope), this can be valuable scavenging indeed. They fight off a couple other parties that are also trying to seize this treasure, including pirates with a flying ship that can plane shift 1/day; that troll from level 1 making a guest appearance as one of the pirates, having since taken levels in Conduit of the Lower Planes and not happy to see the party. Fortunately, he teleports away before getting killed, which is more than we can see about the rest of the pirates.
As it’s been four months since the deal with the Archdruid, they decide to check up on how reconstruction’s doing. Everyone on the continent is dead. Apparently the Archdruid was brought back to life within a week of his defeat, and since the party had essentially left that Prime world immediately, he lost virtually no momentum. Searching a bit, they figure out that after finishing that continent, he had begun to move his forces to the world’s other continent, where fighting had been in earnest. They put a bit more effort into this one, immediately sticking his corpse in a bag and tossing it into the plane of lava, followed by periodic check-ins with the prime world to see if he pops up again. It’s during this time that Naught is killed and the player wants to make a new character (Chel), so the cleric gets the message that the warforged chooses to not be raised. As said character was wearing one of the Four Demon Brothers, they can’t help but notice that the item itself turns to dust, and after they bury the body, the grave site collapses and fills with blood. They ignore this sign and continue.
They fight Twilight’s archnemesis, an interplanar necromancer of no small means
Once that's out of the way, they assist Twilight in her quest, finding out that the person who slaughtered her clan was a necromancer. They follow the divinations to an entity named Duke Blackheart Soulsteal, the Lich of Bladereach (not the one Othar's associated with). They go there, find a mindless/soulless member of the Bewear Bear Clan following Blackheart's commands, along with a number of other fiends. Duke Blackheart himself turns out to be an animated skeleton (not undead, but some kind of awakened construct) who is absolutely not capable of having killed a clan of were-dire polar bears. Interrogating the castle's servants reveal that the soulless dire polar bear just walked up one day to the castle and followed Blackheart's orders, the Duke himself kind of confused as to why but not one to look a gift bear in the mouth. When they destroy Duke Blackheart, something in his chest disappears, and divinations about where Blackheart is updates to somewhere in Gehenna (and that the Duke Blackheart they destroyed was a literal pawn to redirect divinations). When they return home to assess the situation, a simulacrum of Blackheart arrives to warn them against continuing to mess with him and his houses. They kill the simulacrum and rush back to their base, finding a summoned Elder earth elemental smashing their tropical island home (which they kill). They do some reconnaissance, bribe an erinyes, and sneak in through the backdoor to Blackheart's home base, eventually reaching the summit...where Blackheart is hosting a farewell soiree, with all of his friends having been invited. There's even a lich doing standup comedy. Disappointed that the PCs don't want to delay the fight, he opens his shirt and lets Twilight do a coup de grâce on him, his soul visibly ripping itself out of his body and dissipating (contingent spell of some kind). The various entities at the party take their cue and file out, taking gates from the erinyes bouncers to return to Finality. The lich comedian hangs around a bit before leaving, himself a divination specialist, and casts a single spell for them as a freebie; they ask about the Four Demon Brothers. He checks, tells them that one of the four is complete, and is coming for them right now. Ominous signs start appearing, and they’re told that once those appear, the Demon Brother will arrive in seven rounds. The party rushes to Sigil, seemingly safe from its approach, and figure out that they generally have about a three hours before signs appear again whenever they (the three PCs with the demon brother artifact items) leave Sigil.
They resolve the dangerous artifacts, awaken a forgotten god(s) of kuo-toa, find more information on the background of Chel in Acheron, and explore the Plane of Force
The party goes forth and seeks out entities who have ideas of how to deal with the Demon Brother. They find and explore the dreams of an ancient Elder Thing cleric, get attacked by primordial angels who are trying to kill them and take their artifacts before the Demon Brother gets them, convert a community of kuo-toa to worship a forgotten good deity of their race (from before their decline) to get access to said deity to beseech aid in fighting the Demon Brother. There’s a big fight scene, and ultimately all of the demon brother artifacts are removed and this situation is dealt with.
Chel wishes to explore their heritage, so some rumours are explored. They find record of more like her kind in Acheron. There, they find a factory being run by a villainous maug called Malagi of the Thulkarr; discovering that Naught was an early model creation that escaped before memory installation had occurred. They get a pile of Concentration, beat up his minions, and prevent him from being hired out by outside forces for military use.
They pick up a plot hook to explore the mysterious Plane of Force, where they hear about a noble hosting a tournament with the grand prize being the Sword of Gorum, whom the oracle of the party worships. They attend/compete in the tournament, who is hosted by some kind of Force-plane genie, their competition being various genie nobles. They do some socializing and win the competition, getting the Sword of Gorum - a magical sword that can turn into a maiden, the prize technically also being marriage. She says she’s the key to control the Training Grounds of Gorum, a realm thought lost. It had actually been taken over by a fallen spirit of war named Malchai, who is now seeking to become the demigod of genocide. It’s at this point, attempting to infiltrate his realm in Acheron, that they acquire Carnival in the party who wants to take out Malchai for moral reasons. They get past Malchai’s followers; artificer cyclops twins, an army of bladeling warriors, a pair of axiomites (one gives the party a pocketwatch), a pain devil, and a medusa jailer that’s filled a literal colosseum with those who have fought against Malchai. With Malchai’s defeat, the oracle activates the realm’s defenses with the Sword and banish all of the bladelings. It’s at this point the oracle brings in his followers, takes the goal of slowly converting the realm to be fully in alignment with Gorum, and have it slide back home to Ysgard. This is where the oracle retires.
A really big event that’s recent is them dealing with an entire city of archons that threaten untold number of realms in their destruction due to them not knowing the demon artifacts from earlier had been resolved
Going back on old plot points, they revisit a hook. Back in Elysium, where they got the Four Demon Brothers, there was a pin with a city built on the head of it. They wish to explore it, and figure out that it requires quite a bit of magic to shrink down enough to explore. With some research, they figure out the components they need to research a spell that can shrink the party sufficiently to explore a nanoscale city. One component is at a magical university called Unseen Praxis, and Suvesas joins the party at this point as one of the elder members of the society. When they put in the request for the special research item (essentially a minor artifact microscope), they find out it’s been stolen. Doing some divination, they find out that the minor artifact is on a distant Prime world, possessed by a powerful drow wizard. This requires a full quest, as the wizard is sequestered inside quite a bit of magic and has cursed the land around his tower from intrusion. After more than a few fights and such, they get within his sanctum...at which point he goes “oh, that? Here you go! Some guy gave it to me, asking for me to research a shrinking spell for him, which seemed like a fascinating idea, so why not?” They confusedly, but happy to not fight what they think to be an epic wizard, take the artifact back (he’s done with it, anyway) and return to Unseen Praxis. There, they research the spell, go to their tropical base where the pin city is stored, and begin exploring. It’s a city filled to the brim with primordial angels, all doing paperwork in a dizzying amount of complexity. Exploring, they find out three things; the thief of Unseen Praxis had already obtained the shrinking spell from the wizard and explored the place, its power source is incredibly sensitive (simply entering the place caused it to break, and they can’t tell if it was because of them or the thief), and the angelic city is preparing to attack the multiverse with an army of thousands of souped-up lantern archons. The latter is for raw materials to make more, since their power source is gone, and the city had been building the army ever since the party first got the Demon Brothers on them in Elysium. As no individual angel knows what’s going on, and they’re unfamiliar with the paperwork to interface with the city, they seek the original city architect...whose nameplate had been stolen by Hrundlefrost. Thanks to time-sensing divination, they still get the name, and make a mental note to seek Hrundlefrost later (and promptly forget). Their divination to locate the architect fails, so they go to the good kuo-toa god from earlier, who’s still licking its wounds from battling the one Demon Brother. It gives them an artifact that allows one to cast discern location even through the likes of mind blank. They find the entity, a sad celestial of unknown origin but undeniably ancient, having been one of the original entities that first bound the Four Demon Brothers. This entity tells the city to stand down before it goes paperclip maximizer on the multiverse, and asks them a single favour in return: make sure this one family on the Prime has enough to eat on Christmas
They’re just now completing a quest on the Prime, indirectly started by a primordial celestial, to destroy an ancient artifact that Twilight’s goddess wants destroyed. It’s extra difficult, because the artifact had been tinkered with by a mysterious lich known only as the Worm Queen.