Weight + velocity= penetration. Expansion is meaningless without penetration.
That is true, but apply that to any situation, and the 454 Casull is probably the best choice. But there is always the problem of over-penetration. That is why so much research goes to a bullet that offers both, sufficient penetration, and sufficient expansion. Niether is good without the other, you might say. So my preference for a home/self defense round would be the 45ACP combined with a 230gr. Gold Dot. That would offer excellent penetraton because of the weight (and moderate speed) + bullet design, and good expansion, because of the huge nose cavity. I also like that combo, because I wouldn't want a round that is supersonic; that is what would hurt your hearing more than a sub-sonic round. But if the perp is wearing smuggled body armor, then you'd better be a fast and accurate shooter. Several rounds pelting him would definitely knock him sensless, and possibly off his feet, giving you an advantage. I suppose the better thing to do, is with an 8-rd magazine load four HPs, and four FMJs just in case. Or having someone with a shotgun for backup would be helpful.
As good as the modern bullet designs are, they are not 100% reliable 100% of the time.
Sad as it sounds, there is no magic bullet that would offer 100% of everything. But they can come mighty close. That is the purpose of ballistics testing, to find a proper combination of those properties, and make them as reliable as possible. The only thing the shooter is able to control, is time of ignition and the general direction of the bullet. Once it is fired, its all up to bullet design, integrity, and consistency to do the rest. Unless.....? Patriot