I've been reading over the replies here and I've seen a lot of my own sentiments echoed in other posts. That being said, I still don't think it will hurt to add the list and offer my own take on things.
I bought Dungeon Siege III to play with a friend, and knowing full well that it would be different from previous titles in the franchise. I haven't tried single player at all yet, so I can't say much about it. I've thoroughly enjoyed the game so far (we just made it out of the swamp), but we actually find it rather difficult to actually play the game. Because of:
I play as Lucas, and my friend has tried switching between Reinhart and Katarina. Due to his desire to often be away from enemies and my desire to always be near them, we often find ourselves at opposite sides of the viewing area available to us. This presents us a variety of issues: he loses the ability to effectively dodge any enemies attacking him (since he can't move backward, and with the tightness of most areas, often can't move to the sides); I get pelted by ranged enemies that are off-screen and can't move forward to engage or even see them to avoid their attacks; we constantly get stuck on the terrain as we move around during combat, especially in dark areas where the objects blend in closely with the ground (the Crypts most readily come to mind - the stairs there were rough on us, too); with him playing as Reinhart, I also found it hard to see while he was doing his sweeping area attacks. We don't have much screen space available, and his attacks took up nearly a quarter of my screen (often the part directly on top of my character, as that's where the enemies usually were), and couldn't see my own character or the enemies through the animation; and this is minor, but from time to time I want to zoom in to look at my character or the area a bit better, but can't.
Playing on Steam, the game has built-in voice chat that we haven't found a way to disable. We both use Ventrilo on a separate audio device (game plays through the speakers, voice through the headset). Muting him once in-game works just fine, but an option to disable voice would be useful.
It's already been mentioned that the painfully awkward controls are being addressed, so I won't bother with them.
This may be just a control issue, but the ability to be able to walk forward or strafe (or even just the ability to strafe) while blocking would be amazing. Rolling is imprecise and, honestly, it feels really weird rolling everywhere on the battlefield. It'd be great if I could instead approach a group of enemies with my shield out, warding off attacks until I was close enough to attack. Not exactly sound focus-wise, but it feels more natural.
Speaking of rolling, why is it faster than running? Why run anywhere when rolling there is faster?
The stats themselves are all easily understood after quickly perusing the built-in help. What is not is how much stats are actually helping you. It's impossible to judge the value of an item when you don't know how much a particular stat is going to help you.
-Menu / Store UI
The menu and store UI are all around rather clunky, but that just takes some getting used to, like it did in Borderlands (which I felt also had a undeniably "consoley", awkward feel to it with a mouse / keyboard). I don't have any specific suggestions here other than for the store: add a better item comparison window. I can see all of the stat changes between pieces, but I often find myself wanting to actually LOOK at the pieces I have on without closing the menu, which I can't do. And I don't know if you can sell back at full value immediately after purchasing an item, but we can't, we need to be able to. With multiple people purchasing from the same pool of position-adjusting items, misclicks happen.