UT's Bio Rifle is one of the coolest weapons in any shooter. Particularly the alt-fire: charge up, wait for some unwitting sucker to stray into your path and slime 'em!
I have always liked the bio-rifle, but I think Unreal Championship 2 does it the best.
Primary fire shoots "smart" globs of goo that bounce after enemies for a short duration. Secondary fire is a press and hold affair that shoots one giant glob of "smart" goo. (One thing to note about the "smart" globs though, they will go after you if there are no other enemies or you cross their path.)
Here's the really nifty part though...
While holding down secondary fire, you can also launch the glob of goo by pressing primary fire. If you do this and let go of secondary fire while the glob is airborne, it explodes and forms a poisonous cloud.
UC2 has this level of functionality for nearly every weapon. For instance...
You can "freeze" shock balls from the Shock Rifle for a limited period of time and use them to get the drop on unsuspecting foes coming about a corner by using the shock combo.
Secondary fire for the Ripjack energizes the blade causing it to explode upon hitting something. Using it in conjuction with primary fire allows you to place the blades so they function like proximity mines.
The tarydium minigun gradually begins to heat up, causing the gun to fire faster and the shards to do more damage. With proper timing, usage of the primary and secondary fire causes the minigun to fire at advanced speed from the get go.
Oh and this will be even more offtopic, but...
We really should all get together and play Malice online some time. I've played the mutli-player once, but I don't remember what it was like all that well.