Will second the King of Tokyo and Munchinkin votes...Smashup is also great and Forbidden Island and Castle Panic.
A card game that is a ton of fun, and cleaner (if you don't buy the R rated expansion) is SUPERFIGHT!
Basically, You have white cards and black cards...the white cards are heroes the black cards are powers of handicaps...the dealer randomly places a white card and two black cards and everyone else tries to defeat him with a white and a black...then plays a black handicap on the player to the side of them...
SO you could have:
Chuck Norris, with a jet-pack, armed with The One Ring
and to beat him you play:
Girl Scouts, In a Beserker Rage...but your neighbor added to you: Made of Peanut butter...and so on...around the table.
There are expansions that add extra geeky cards, kids favorites, and the r-rated ones (which are still less offensive than Cards Against Humanity).