M.L. Martin
Hero
The cyncial part of me wants to repeat its prediction for 4E and say "The DM." 
More realistically . . . hmm. Nearly every 'sacred cow' left is part of the game's identity and the larger genre it's created--clerics, Hit Points, and the like come to mind--to the point that abandoning them would make the game less familiar to the larger target audience that's grown up on things like Final Fantasy and World of Warcraft. And the d20 will by that point have over a dozen years of marketing as part of the game's identity behind it.
Random damage is one of the only things I can see going away at this point, with the randomness relegated to the hit/miss chance, possibly with an expanded 'margins of success' mechanic based on the critical hit mechanic. That would also allow them to reduce the dice down solely to a d20--or even 3d6 if they want to sacrifice the iconic status for greater accessibility.

More realistically . . . hmm. Nearly every 'sacred cow' left is part of the game's identity and the larger genre it's created--clerics, Hit Points, and the like come to mind--to the point that abandoning them would make the game less familiar to the larger target audience that's grown up on things like Final Fantasy and World of Warcraft. And the d20 will by that point have over a dozen years of marketing as part of the game's identity behind it.
Random damage is one of the only things I can see going away at this point, with the randomness relegated to the hit/miss chance, possibly with an expanded 'margins of success' mechanic based on the critical hit mechanic. That would also allow them to reduce the dice down solely to a d20--or even 3d6 if they want to sacrifice the iconic status for greater accessibility.