A large part of that CF reliability is FEEDING. Its not just more reliable ignition than a rimfire. Remember that back around 1900 and for a while after, center fire ignition was not as reliable as it is today.
One of the reasons the .25s and even the .32s are useful is that they nearly always work. FMJ ammo and centerfire ignition are as reliable as it gets.
Often the lead .22 bullet will do more damage than a .25 cal FMJ in a human body, because it flattens, expands and may veer off course.
In my experience, here is no other firearm as temperamental about feeding as a semiauto .22LR pistol. Some will run well on any or everything. Some won't. Some will only run well on one or two brands/types of ammo. Some won't even do that, reliably. If you have one that runs well on something great. But if you don't? Then what??
When talking personal defense, which is better, something that punches an ice pick type hole every single time, or something which might do slightly better now and then, and maybe jam on the next shot?
If a bullet reaches or passes through a vital spot, small differences in energy and diameter don't seem to matter much. If it doesn't having reliable follow up shots is very important. Over all, as a group, semi auto .22s are just not as reliable as centerfires. Individual guns may differ.