I have 2 "go-to" home defense guns . . . a S&W 627 8-shot .357 magnum and a Wilson CQB 1911 .45 ACP. They're in different parts of my home and accessible quickly. Both are guns I shoot a lot (and extremely well), both have also been 100% reliable.
My second instinct is to choose the pistols I love to shoot and they are 1911s and BHPs. I enjoy the accuracy and power of the 1911s and there is no handgun I shoot better and faster than the BHP.