Horribly balanced game. Some skills and guns are horrendously overpowered, especially in tandem, while others have barely any impact. Some enemies hit/tank like dump trucks while others seemingly fall over in the wind. Bosses are pretty universally lame. I understand it's challenging to properly balance this sort of thing, but c'mon. It's a big game, sure, but it's not exactly WoW.
For the sequel, I'd just like to see more parity with guns, classes, and skills and a nice, even difficulty curve. Oh, and the ability to play 2-player split-screen on-line.