With that sound logic, I think you could do well with a Ruger Standard Auto. It is highly reliable too and easy to load and use. It's not light but not too much to lift and aim, recoil is slight. Use hollow points for social work and anything for inexpansive practice.
NOTHING is very useful for home defense if you aren't so well experienced with using it that you can do it almost without thought of the weapon itself. Any center fire is MUCH more expesive to shoot than a .22RF, it's about the same cost as reloaded centerfire ammo!
This is the one I would recommend. Years ago, I bought a Taurus PT-22 for my wife because of her RA deformed tiny hands. With the tip-up barrel, she wouldn't even have to rack the slide. She tried, dammit, but alas, she couldn't even work it, as her hands are now all but useless. Had she had larger hands, or even a bit more dexterity, I certainly would have liked that Beretta, as it's chambered in a decent defense caliber.She also has a Beretta model 86 in .380. It's a relatively large .380 which helps with the recoil, but the nicest feature is the tip-up barrel which means you never have to operate the slide.