The mooks are way tougher than before. The blue Drudge that popped out of egg sacks in the first game can now kill you in 5 hits, on the lowest difficulty.
The shotgun's pretty underpowered. Don't use it.
Oh, god, the ending. I've never laughed that hard at a game's ending before.
Ford kills Adams and the ASE absorbs his soul. This signals a spaceship in another part of the galaxy to come to Earth. Seconds later, George Washington and Abraham Lincoln step out of the conduit and say "We're here to help!". To top it all off, the ending achievement is called "You're Winner!"