Bigger is not necessarily better. There's this weird notion that somehow something 'magic' occurs when a .45 is used, but that everything smaller is somehow less lethal. I would argue that all the calibers are quite lethal, but they all require dedicated tactical efficiency...and tactics can vary.
A lot of folks seem to advocate a .357 over a .38, but firing a .357mag from a little J-Frame is a bit masochistic - and I would argue that a J-Frame is more efficient when its firing .38's...and the shooter is more likely to fire .38's from a J-Frame more efficiently. Two rapid well-placed shots from a .38 beat one big not-so-well-controlled shot from a .357mag. At close range a .38 is not exactly an anemic round.
In regard to .25's, .22's and .32's...I'll just say that someone who knows how to shoot them with confidence is not exactly naked - and at close range, well, they can kill a person quite nastily. If I've trained well to rapidly and accurately pop off 7 shots from a .22 at a bad guy who is 5ft away, I'm a few steps ahead of the person who has a .45 but who hasn't really trained to rapidly fire at anything in a close quarters situation.
It comes down to training and proficiency and two mechanical factors:1)power ie. the ability to deliver energy 2) controllability ie. less recoil and the ability to rapidly draw and fire. The snubnosed .38 is hard to beat. It draws quickly. It's concealable. It delivers a powerful but controllable round.
One can step up the power and go up in caliber, or one can step up the controllability and go down in caliber. Whichever direction one goes, there's the challenge to become proficient in the tactics to be used.
At the extreme end of controllability is the .22/.25acp ie. it's as light as a toy and has no recoil. It can be whipped out and fire 7 shots in less than 2 seconds. It's extremely concealable. At the extreme end of power there's .40S&W's and .357mags and one reasonable shot will usually be all that's needed. In the middle is the ol'.38.
One nice aspect of the SP101 in .327mag. is the .327 mag. has the power of a .357mag. - but it can also shoot .32longs and .32H&R mags. - so in theory one could plink and practice with it in .32's and .327mag and have the best of both worlds. My biggest beef with the .22's/.25's is not so much the caliber size inasmuch I believe revolvers are better than semiauto's for close quarters self-defense.
The revolver is less likely to malfunction. When one's adrenaline is rushing, the revolver is more controllable<especially to someone not as experienced>and the revolver is more easily fired from a weakened hand.
I would not pick a .22 revolver because ironically the trigger pull is likely to be heavier than the trigger pull of revolvers used on centerfire rounds. A .32/.327 or .38/.357 would be my top choice.
However, there's times when concealability is what's really needed - and a Seecamp or a little .22/.25acp is the most concealable. There's lots of choices - lots of viable options to fit one's needs.