For the sake of full disclosure, I never played the original Sanctum. The 2011 title from Coffee Stain Studios was one of the first games to blend together the tower defense and first-person shooter genres. But you don't need to have a full knowledge of the series to appreciate what the Swedish indie developer has created. Sanctum 2 offers a superb shooting experience, though one that's meant more for friends than solo players.
Sanctum 2 pits humanity against your standard alien invasion, with the story unfolding through static comic book panels. Players can pick between four character classes, each outfitted for a specific play style. Waves of enemies will come at players, with new resources appearing after each wave has been eliminated. Solo players will likely have a tough time deciding between classes, but a well-balanced team of four should be able to take down these waves without much trouble. All the weapons are easy to use, but there's an iffy reloading mechanic that requires players to hold a button, which can be troublesome when coming under fire.
In terms of hybridity, Sanctum 2 is built more as a shooter than it is a tower defense game. Resources are fairly scarce and players don't get much to work with in-between waves. Since towers don't often cover a large area, it's up to the players to put their shooting skills to work. Unlike most tower defense games, however, the enemy aliens won't simply run blindly down their path. Many of them will respond to human fire and will lunge at players with specific attack patterns. In this sense, Sanctum 2 plays more like a standard horde mode, especially once friends get involved.
Players don't necessarily have to dive into Sanctum 2 with friends, but it's dangerous to go alone. Campaign stages won't adjust themselves for solo players, which creates a bigger challenge late in the game. For example, some of the later levels will have aliens attacking simultaneously from three or four different fronts. With towers only able to get set up in so many places, I wasn't able to split my focus in so many directions and the center core was destroyed before I knew it. It's one of those situations where partners would have helped, since one could have guarded each front or one could have guarded the core. I enjoyed playing this game with buddies, but it would have been nice if some of the stages could have adjusted themselves whenever I wanted to fly solo.
Fortunately, buddies can jump in and out at any time, as all games are played in an online setting. The drop-in, drop-out mechanic proves to be a nice touch, as I could simply wait for a public player to jump in whenever I was feeling overwhelmed. There was also an option to set the server to private whenever I wanted to dive in with friends, but there was no option to play offline, which proved to be a bit of a hassle. I found this out the hard way when I attempted to pause the game, only to find out that I was still getting attacked through the pause menu.
Connectivity issues aside, Sanctum 2 is a perfectly competent shooter. It doesn't necessarily revolutionize anything in either the FPS or tower defense genres, but there wasn't anything it actively did wrong. Coffee Stain Studios' latest title is simply a fun game to play with friends, with not much more to it than that. Anyone looking for a good multiplayer experience should set aside an hour or so and give Sanctum 2 a look. 
This Sanctum 2 review was based on a Xbox Live Arcade version of the game using a digital code provided by the publisher. The game is also available on PC and PlayStation 3.
Ozzie Mejia posted a new article, Sanctum 2 review: friendly fire.
Sanctum 2, from indie developer Coffee Stain Studios, doesn't revolutionize either the tower defense or first-person shooter genre, but it does offer up some fun for groups of friends.
My friends and I liked the first game so we bought the new one. It feels like it took a step or two back with tower limits and such. Also the 2D TD game bundled with it crashes all the time especially when I'm about to win a level on hard.
I dunno about the console versions, but on the PC you don't need to hold down the button to reload. I always just tap the R key to reload.