I'm going to stick to things I actually know about, rather than what I'm speculating about. There's a lot of stuff I like, but there's a couple of things that feel like WotC bugged my house to find out my D&D wish-list. And a couple that just bug...
Favorite (2-way tie):
1. Basically dumping the tired old pseudo-Vancian magic system.
2. More emphasis on intrinsic powers for characters and less emphasis on their gear.
Least Favorite (2-way tie):
1. There's been some indication that the game will move even more towards flashy, superheroic, almost X-Men style flavor (short-range teleports and the like). I prefer my epic fantasy to be a little more grounded in "the real world" (i.e. more Lord of the Rings and less Eragon).
2. They've kept the arcane/divine spell divide, which I hate. But I concede that it's a longtime trope of D&D.
I'm hopeful that I'll be able to houserule away the things that bug me. For example, with the option of non-divine healing, I might be able to design a world where gods don't interfere and priests don't cast spells.
I guess I just hate clerics...