I really like the way EverQuest II handles it. A sort of hybrid of d20 Modern and D&D by way of the MMORPG audience. Four base classes (Warrior, Mage, Rogue, Priest) and then a bunch of advanced classes that spring from those. Talents a la True 20, feat chains, stuff like that. Niche protection by advanced classes but simplification made possible through use of just the four base.
I suppose you could also do the Warrior/Expert/Adept route of True 20, and then add the advanced classes, but I'd want that 2-stage element to it.
If the EQII RPG had only been handled better than it was, I'd be all over that.
Cheers,
Cam