I'm looking for some advice on people's favorite large board games. By Large Board games, I am referring to things such as Descent, Arkham Horror, World of Warcraft Board game and many others. I own Descent and I am looking for something else to add to my repertoire.

What I AM looking for;
Games that relative RPG novices will be able to learn in a day. I don't really want something that takes 16 hours to explain to someone who may not have any knowledge of these particular type of games.
A game that takes around 3 people to be able to play, which is not to say it can't support more players, but I would rather not have a game that you MUST have 4-5 to ever play with any enjoyment.

NOT looking for;
Games that take a day to set up and/or play, I'm looking at you Axis and Allies...
Games that a super cutesy, Munchkins is about as far as I will go in this particular direction.

If I think of more things to add to this I will, any input is greatly appreciated.