Epic Spell Wars of the Battle Wizards: Duel at Mt. Skullzfyre. Ideally you want four or five participants but it plays just fine with two.

I will confirm this recommendation. I bought a copy from my local Barnes & Noble and have found it to be good fun and a rather intense late-game playing.

My first game was solo because I couldn't wait to try it out, and at the end I still had 3 towers standing.

My second and third games were both with three other players, and at the end we had only one tower still standing, and I was dead last in points because I had spent almost all of my turns injuring incoming threats so the others could kill them.

My copy of Infiltration arrived last week. It plays well with two though each player uses two characters instead of one.

I'm majorly stoked about the release of Netrunner under FFG's Android brand. That's one of the all time greats of two-player deck building games. That's one of three purchases I hope to walk away from GenCon with.

I'll confirm Doc's confirmation, had a lot fun playing Castle Panic with two players.

I'd go with everyone else suggestions.

My wife and I also play several games together.

My wife (non-gamer) likes most of the suggested as well as adventurers and gears of war (a cooperative game) both by Fantasy Flight.

We just got one published by Kosmos, called Lost Cities.

It calls itself a Daring Adventure for Two.

I don't know about daring, or adventure, but it's fun and the artwork is good. You have a set of five destinations which you reach by playing the right suit of cards numbered two to ten, and you don't have to play all the cards in that suit but they do have to be played consecutively, and when the last card is drawn you tot up the score. So it's a numberchasing game dressed in pretty pictures. Gamma-Ray likes it more than I do, and I don't find it "daring" or exciting, but I do like it.

It also has suggestions in the back for converting it to a 4-person game, which was thoughtful.

My son and I have played a ton of Quarriors and loved it enough to pick up the Quarmageddon expansion (which is so worth it, that custom dice tray makes set-up so much easier.)

If you like games with lots of custom dice where the rules and strategy change with each game, you'll love the huge replayability value of Quarriors. The 'board', known as the Wilds, is made of cards and the various cards each have different rules for the monster or spell that they represent. So, each game has a wide variety of critters that you can recruit and summon for battle.
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TAZ

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I'll second this one. I really enjoy Lost Cities.

Has anyone mentioned the LotR LCG? My friend bought this a few months back and you can play it solo or with 2 people. It's fairly difficult, but there are expansions to add encounters and allies.