The 1st is the targeting system. I played D2 and I like so much that system, but in D3 I see some "movement and attack" problem, this is one of several threads in us.forums that speak about it:
Diablo 3 Targeting vs Diablo 2
The 2nd problem is the possibility to swap skill during the game, in a bad UI also. I think the game will be a lot less fluid, and not good overall. I suggest to eliminate the possibility to swap a skill during a single dungeon or a single mission.
That ruins also some slightly RPG aspect of the game.
This is one of several threads about this argument:
Skill swapping is too easy/fast
Tell what do you think about. I don't like D3 atm, in my opinion these two aspects are really important to fix, I'd like to hear some critic but constructive messages about it.