Whether that familiarity is important enough to justify compromising game design is of course debatable, but that's not what I want to talk about. I just want to try to identify what problems remain after Tomes, which of those are fixable with evolutionary means and what those means might be.
As minor problems I'd classify for instance aspects of the skill system, fear mechanics, grappling, some broken spells, charisma not being important enough, crafting discriminating against non casters and finding a good way to deal with fractional BAB/Saves without needing a calculator.
As unfixable problems while keeping the mechanics familiar I'd classify for instance Five Moves of Doom, paradox of choice and too much rolling/interrupting. It can be mitigated, for instance additional classes could use WoF mechanics, you could give only a single extra attack from BAB, make haste/speed work differently and remove celerity, contingency, foresight, cheap ways to quicken spells ... but ultimately people will expect the Vancian casters to have Five Moves of Doom and roll lots of d6s for damage, and the fighters will need their AoOs (they are of course a 3e invention, but I think a still necessary one ... they were the natural replacement for simultaneous actions, which I don't think we want to bring back).
So, in my opinion fixable Problems :
- Rocket launcher tag.
- Focus fire, for when for some reason rocket launchers don't kill at once.
- Pure damage has been boosted to near rocket launcher status in and of itself, which is necessary to avoid padded sumo.
- It's smart to use your most powerful abilities on round 1, which creates a lack of dramatic build up in combat.
- PrCs while fun for us lego enthusiasts, and a great way to sell books, were too constricting.
- Too many bonuses and item slots.
- Slaughter is the default option in combat.
Potential solutions :
Although I'm not a fan of the word CAN ... maybe Morale? (A bit iffy for mindless opponents, but meh.)
Paths are probably a better replacement for PrCs, something which just comes in addition to normal class progression rather than replacing it. Maybe even a generic gestalt path for dual progressions for which no specific path has been created yet.
For too many bonuses, you can remove all the standard bonus items and compensate for that elsewhere and then reduce the item slots ... but it doesn't help with the bonuses from buffs ... a limited set of buff slots perhaps? Or is that too MMO?
To prevent slaughter just allow massive amounts of negative HP before someone dies and provide more alternatives for the true killer SoDs which just take opponents out of the fight ... make slaughter an evil choice rather than a smart choice.