Crank 1: Chev Chelios is poisoned, and must maintain his adrenaline while hunting down his poisoners. Causing violence keeps his adrenaline up. Mayhem ensues.
Crank 2: Chev Chelios has his heart removed, replaced with an artificial heart that must be charged with electricity. Chev does violence near sources of electricity. Mayhem ensues (much worse, less clever mayhem than the first movie).
Crank 3!: Chev Chelios has a special part of his heart and brain removed, replaced with (whatever). Result is that he must keep empathizing with things, while he tracks down his enemies. If he stops empathizing, he dies. Examples: recognizing his own improbable durability in the wilting of a perennial flower; watching a father teach his son how to throw a football; listening, really listening, to his friend Kaylo/Venus talk about the difficulties in maintain a stable, respectful relationship. Chev must do these things while still beating the crap out of a bunch of (ethnic) gangsters. Mayhem ensues.
Seriously, Brian Taylor and Mark Neveldine, think about it. I would actually see that movie in the theater, instead of waiting for my friend to buy the used DVD for $4 at a Blockbuster.