The only GOOD solution at this point (AFAIK) is the unlimited ammo cheat.
The reload thing they built into MAME recently "almost" works.
It is designed to move the cursor to the (0,0) coordinate, and then fire.
It usually fires before it completely gets to (0,0) though.
The reason the "fire off screen" reload doesn't work in most games is that the Act-Labs gun fires at the last aim point if you press the fire button when it can't see the screen.
There are some arcade games that let you use the reload button.
I can't think of which ones at the moment, but they ARE out there.