Well it was definitely originally intended for 4 players, and plays best that way. None of it is balanced for two player play, and it would just become a race to see who achieved their goals first. Three players is tough because as soon as they decide to gang up on one person, there isn't much that person can do. Four is ideal, but it also works with 5 or 6, assuming you don't mind playing a two or three hour game.
I'm lucky that my new roommate is a giant nerd (literally, he's an ex army ranger and amateur power lifter, he's huge) and has been asking me to learn. We have one other friend that I know I can rope in. Ideally I can find one more to get a good game going.