Style plays a big part in my selection here, but taking out enemies instantly from across the map with a shoulder-mounted laser cannon is a hard feeling to replicate. And which version of the Spartan Laser is the best?
Clearly the Halo 3 Spartan Laser. You get more shots overall, it takes some finesse to use, and it will destroy anything and everything that crosses its path. It doesn't matter if you're in a tank, Ghost, Banshee, or just waiting around a corner. If the Spartan Laser comes your way, you're dead.
Give up hope all who see the red beam of death.