I guess military counts, so I'd have to say it would be a 20mm MK-12 aircraft cannon. We had a bore-sighting range for A-4 Skyhawks, and like any other weapon system, they had to be zeroed on the range.
Biggest hand-held, would be the M-79 grenade launcher. Biggest rifle, M-1 Garand and the biggest handgun I've fired is the Ruger Super Blackhawk .44 mag, with 7" barrel.
