The little .22 short is both our oldest, and our smallest American metallic cartridge. Designed by Smith & Wesson, it has been in continuous production since 1857. The initial loading was a 29 grain lead bullet and 4 grains of fine black powder; Modern "high velocity" smokeless powder loads develop 850 feet per second or so, even from short pistol barrels.
In the words of the late Frank Barnes, "The .22 short can be deceiving because it looks small and relatively harmless. When fired from a rifle it can penetrate 2 inches of soft pine and has an extreme range of almost 1 mile. It can seriously wound or kill . . . right up to the limit of its range. Be careful! Make sure of your backstop before shooting any .22 rimfire."
Coming along a century later, the big .44 Magnum was a joint Smith & Wesson and Remington Arms development. Intended for hunting, it launches a bullet eight times as heavy, and more than 50% faster than the little short!
Here you can see the size difference of a Beretta Minx in .22 short, and a Ruger Vaquero in .44 Magnum. What you can't see is how much lighter the featherweight Minx is! While compact for its power, the Ruger is as heavy as a brick.
We would all prefer the big .44 if the chips were down, but it can't help you if it's not within reach. Way out in the "wide open spaces" you just might be able to pack it, but the average city dweller can't.
The little Minx, though, CAN go along - anywhere, anytime - with anyone who has bothered to obtain a concealed weapons permit, as it is light enough to be literally forgotten by the wearer. That's the reasoning behind the tiny cartridge it fires, designed as a self defense round 150 years ago! In pistols, POSSESSION trumps all else. A truth which bears repeating is: a pistol can't help you if it's not within reach, when you need it.
Of course, the examples shown are at opposite ends of the power spectrum. Our Army once estimated that a projectile needs around 60 foot pounds of energy to incapacitate. While the Ruger can deliver ten times that amount, the little Beretta just can't get there. The two obviously require different tactics.