A GREAT question indeed. The one that I would choose for hunting and not look back is the Ruger Vaquero, blued, five and a half inch barrel in .45 Long Colt. This cartridge is very flexible! It can be loaded to approximate the 44 magnum with less recoil and pressure. It can in its factory loads be used for plinking, target practice, etc. The one that I would choose for self defense is the VERY SAME gun! Why? For the reasons mentioned PLUS it is a wheelgun, and therefore less likely to jam. I didn't say it is not guaranteed to malfunction, but it is undeniably less likely to do so. Under the pressure of a self defence situation, dependability is an absolute necessity. My second choice as a self defense handgun is the CZ 97B, .45 ACP. It is a rather large pistol, but it is very reliable , and extremely accurate! The weight helps with controlability, and having large hands, I have no difficulty with gripping it.
Kindest regards,
Rifle Man