A head shot (i.e. through the brain, not the face) or a spinal strike are about the only ways to guarantee the vaunted and proverbial "one shot stop". That includes with rifle rounds, not just handguns. The "computer", i.e. brain, or it's "cable" are the only foolproof way to instantly stop a threat. Of course how far down the "cable" will also come into play; you might make them a paraplegic but their hand can still pull a trigger.

I have read of a number of cases (in combat or on the street) where the recipient of a wound was shot right through the heart and was still able to fight back, albeit for a very limited time. Of course it only takes a fraction of a second to squeeze that trigger.