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Once upon a time, the 125 grain .357 Magnum was considered the most effective anti-personnel handgun round. But that’s a revolver, eww.
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See, there's the problem, people don't just want the most effective round, they ALSO want it in the package they want.
They want small and light, for concealment and easy carry, then IF they get that in a sufficiently powerful cartridge, they complain about the recoil.
Or the lack of round capacity, or the size and weight, if the gun is large enough to tame recoil to manageable levels. Oh, and don't forget they want it at a low price.
There's no free lunch...sorry.
I have a pistol that shoots that 125gr .357. Semi auto, 9+1 capacity recoil is not heavy. The GUN is heavy. Blast is fierce. The grip is huge. And the MV is over 1700fps with select handloads from the (nominal) 6" barrel.
No one will choose it as a carry piece, it goes 4.25lbs empty.
It's not "practical" but I like it, as a home defense pistol, I think it would do well, even if you missed, you could beat a grizzly bear to death with it, possibly,...
The real question is not what is the best caliber for self defense, the question is what is the best caliber for self defense in a pistol YOU find acceptable.
And that's going to be as varied as the people answering the question.