Race for the Galaxy is good with just two. We had to watch a video tutorial or two to really grok it. Be haven't had the chance to play with more than 2.
TGC (if you see this): Do you find that once one of you gets ahead, it tends to stay that way? I was sharing this thread with my husband, and he was surprised RftG would be good with 2, since he found it unbalanced that way (ie, once someone gets ahead, it tends to stay that way for the duration of the game).
It's really funny to read the suggestions and be reminded of people's different preferences. Some of the suggested games we find pretty boring for 2 (especially when compared with playing as a group). And simple is usually a bad thing for a game with the 2 of us - we get bored soon if it's not super strategic and complicated. And then most of the super strategic games we own, have better balance with more players.
That said, in case anyone does want suggestions for games that are good for families or groups that don't want to take 45 minutes to learn the rules of a game, we like: Hanabi (cooperative, you stack cards in order 1-5 by color but nobody can see their own hand, just those of others, and you take turns giving hints), Quarto (for 2 - similar to Othello or Go, different shaped pieces and it's connect 4 by height, color, hole/no hole, circle/square), and Bohnanza (super fun, basically trading/negotiating game where you plant beans and harvest for money -
http://www.amazon.com/Rio-Grande-Games-RGG-155/dp/B00008URUS). The first 2 would take <5 mins to explain, the bean game maybe 10mins, but pretty straightforward.