Sanctum is the world's first FPS tower defense game and is set in a beautiful science fiction world. You take the role of Skye, an elite soldier sent out to protect her hometown, Elysion One, from hordes of mysterious alien creatures. To facilitate your success you construct defensive structures and upgrade handheld weapons. Jump right into the fray and wreak havoc with your own weapons - unlike regular tower defense games, you are a key part of the defense. Sanctum has taken the best features of first person shooters and tower defense games to create something totally unique.
Sanctum gets a huge update today (7/7/2011) where 4-player co-op is added to the game among other nice things. Check this trailer to see what it's all about :)