CP3S said:

I actually tried changing my Xbox settings from 5.1 to two channel, and it fixed the problem. Obviously it is a glitch in the game though, I tested all my speakers and they're are working, and the problem didn't exist until after the first time I quit playing and loaded a saved game. So now I have to remember to switch my Xbox back to surround after each ACII session.

Well, at least that's something. Is it enough to keep you from finishing the game?

I read someone's complaint that the vocals dropped out for a couple of hours- they switched to subtitles, and then the voices (in my head) came back (and told me to murder people).

Maybe try 5.1 again after a segment or two?