Biggest pet peeve would be the extra, superfluous 1-15 additional clicks required to do simple menu navigation. If you want to travel to a location on the map, first you click the location to center it on the map, then you click to go there, but, no, now you must click "OK" to, you know, actually go there. If you need to choose companions, it's not just 1-2-3 because it's on a rotating dial, so you have to click all the way over to one companion, then over to another. And if you don't pick 3, you have to click the "yes, I'm old enough to go without a full party now, Mommy" button. If you want to navigate inventory you have to keep clicking "Back" in and out of each category. If you want to reduce the GUI to take a full-screen screenshot, it's no longer a single hotkey but a trek of clicks through the menus to change a setting and return to the main screen (then back in again to restore the GUI). If you want to get an active quest to stop showing on the main screen you can't just click one thing to toggle quests showing or not showing: you have to keep hunting down each new quest that comes up because they get auto-selected as your active quest as soon as a new one arrives. On and on like this... Not a game-breaker, just a recurring source of irritation.
Oh, and another one. There are a lot of clipping issues in the animations- pretty much don't care in the least except for one: Morrigan's hair on the right side. Over and over it clips as you're trying to listen to her- like trying to pay attention to what someone says while they're preparing to eat raw butter or swallow a goldfish in front of you. And the main thing is, it was Morrigan- not some random NPC #49. Where was the QA for a major NPC? And the other thing is- her hair moves. What about my hair! I want my hair to keep clipping on one side too!