I second "
Apples to Apples." I've played this a couple of times in a big group and it was really fun to see some of the pairs submitted.
Cranium is also another favorite, or any of the many variations they have developed. It combines a lot of different elements like trivia, spelling, drawing, and performance so no one should feel left out.
I saw a new one at the store the other day that looked interesting called
Dicecapades. Haven't played it though.