Awesome, but Impractical: The Rocket Launcher. Its ludicrous damage does not make up for the scarcity of its ammo, the lack of enemies that actually warrant its use, and the presence of equally good or better options when those enemies do appear.
The Plasma Gun starts out as Awesome, but Impractical, with very good damage, but a slow burst-fire rate, non-Hit Scan projectiles and Splash Damage that might kill you when used in close quarters. Upgraded, it gains a Secondary FireCharge Attack that fires off any remaining ammo in your clip as an Energy Ball that zaps any enemy in its path, then latches onto the first surface it touches and continues doing the same until it explodes, making it an excellent area-denial weapon in addition to its use as a mid-range pseudo-assault rifle.
BFG: This being an Unreal engine game, all of them. First prize probably goes to the Shroud's "Titan's Fist" energy cannon, only usable by infected individuals.
Boring, but Practical: The Bulldog PDW. It's the first real weapon you get, but you are likely to use it well into the later stages. When upgraded, it attains the fastest fire rate out of all your weapons, with some decent accuracy to back it up. Add to that its plentiful ammo supply and the fact that it deals good damage to virtually every enemy type, and you can see why it's Mason's Weapon of Choice in cutscenes and promo materials.
Enemy Mine: Karina and Mason are prisoner and captor, but are forced to work together to overcome the Scavengers.
Evolving Weapon: One of the highlights of the game (maybe the only one) was the ability to upgrade your weapons using modular "Weapon Energy Cores". Each weapon could be upgrades a total of three times and gained new and impressively destructive abilities as you did so.
Heal Thyself: You have a medical injector that restores one bar of health per use and has to be reloaded like a weapon.
Human Aliens: Maybe. The Shroud are shown to be pale, hairless, corpselike beings vaguely resembling the Necris. What they actually are is never explained.
Infrared Xray Camera: Upgrading the Sniper Rifle gives its scope function the ability to work like this. While it does avert the tendency for this sort of camera to see through walls, it only seems to pick up heat produced by enemies, and not by the surroundings.
Lost Technology: One of Jack's monologues states that the Weapon Energy Cores were once Shroud technology used during the war. May or may not also be Imported Alien Phlebotinum, given that it's not revealed what the Shroud are.
Manipulative Bastard: Colonel Stockton, warden of The Anvil. Not only does he pay the Scavengers to shoot down Mason's ship in order to capture Karina, but he then captures her himself and doesn't pay them. Then he infects himself with The Virus and tries to kill you.
Red Shirt: Stubbs, the pilot of the ship ferrying you and Karina, and the only other friendly face in the game arms you with the Bulldog and helps you fight off the Scavengers for a few minutes in the first chapter before he's unceremoniously killed off-screen.
Sequel Hook: Somewhat unusual in that it's not explicit, but it's definitely there. It's shown earlier in the game that Karina is capable of surviving the explosions she generates, which hints that she may have survived the massive explosion at the end of the game, even if no one else did.
Unorthodox Reload: The Frag Rifle has a vertically-oriented internal magazine, cycling through the shells like a soda dispenser as it fires. Going with that metaphor, reloading it looks like stuffing a six-pack of shells into open port of the gun, before removing some sort of pin that held them all together.
Vehicular Combat: The story mode has a few instances where you can man an armed vehicle, and such vehicles are also available in multiplayer maps. While decent and perfectly playable, these instances seem rather derivative of Halo.
The Virus: A top-secret bio-weapon that grants incredible powers but often at the risk of suddenly exploding. Karina is it's vector, and Mason gets infected during the crash, giving him an excuse to chase after her when she escapes.