Most of your modern shooters have absolutely brutal button number requirements and are essentially untranslatable to arcade controls.
When I play Borderlands my right hand aims and controls 8 mouse functions/buttons (5 buttons, scroll up, scroll down and scroll click), while my left hand handles a Belkin n52te single handed gaming keyboard with 16 buttons, a clickable scroll wheel and a direction hat and I have all of those mapped to game stuff.