I do my best not to buy handguns in calibers that I already own.
I have, on numerous occasions bought a handgun because it was in a caliber I already own. And also forgone purchases that were in calibers I simply didn't want to tool up for.
For instance I've passed on all the .50 cal stuff, even in guns I wanted, simply because of having to add .50 bullets, cases, & dies. Another .44 or .45 for me (or 38/9mm) simply means another neat gun to check out, without any additional ammo related expenses (until/unless none of my usual components gives satisfactory results, which is pretty rare)
Guv, I'm not going to play fair with my answer.
I don't have to choose, I don't need to choose, and I won't choose just one. If there were a credible situation that would require me to only have one handgun (and there is none such that I can see), my choice would be between the guns that have sentimental value to me, (all are in useful calibers) and which ever one I finally settled on (and that wouldn't be easy) would be the caliber I kept.
Now, If you are just starting out, and don't have a battery of guns and calibers collected over 40+ years of handgunning, I can give you my opinions of different things I know about, and what might be best for what you want.
Most people will have all their needs met well with just two, a .22LR and a .357. And the .22 is more convenience than need. The wide range of loads possible in a .357 revolver makes it about the most versatile choice for most uses. Even very big game has been taken with the .357 in the hands of experts. And .38 wadcutters do a fair job on small game, within your ability to hit accurately.
No one gun is best for all possible situations, likewise, no one caliber. Despite my personal affection for big bore pistols, I have to admit that you have to go a long way to find a situation where the .357/.38SPL combination doesn't fit somewhere between "works tolerably well" and "works great"!