Sadwick (I think that's his name) from "The Whispered World" has a terribly annoying voice. Everyone said that you get used to it, and they were right, but using that voice seemed like a terrible decision. It was a hurdle to overcome, and if not for the amazing art could've made me give up on the game. I haven't actually bought it yet, just played the demo, and it kept crashing on my computer. I'm using a different one for gaming now, so maybe it will go better.
Also, April Ryan from "The Longest Journey" is great a lot of the time, but her reluctance to accept magic, her destiny, and her teenagerish attitude is kind of annoying at times. Not the reluctance exclusively, because that's entirely understandable, but there are times when she seems to have accepted it already after seeing clear evidence of what is going on, but then suddenly reverts back to being unwilling with an attitude. I found it a bit jarring.