The most important quality of a self defense weapon is convenience-if it's in your glove box, it's the wrong gun. Carrying a gun, especially in the summer, is a pain in the butt. I can talk all day about the gun I would take to a firefight, but the real question is what gun do you take to the grocery store or movie theatre? For me, the solution is something small, concealable and reliable that I'll be most likely to have when I need it, like a Chief's Special or, my personal favorite, the .44 Bulldog.
A major consideration is the operating environment.
Every firearm has different characteristics. You must analyze the characteristics that you value for your particular use.
The handgun you may want downstairs may differ significantly from what you would want by your bed.
The one you want outside while working in the Yard may be different still.
The one you would carry as a sidearm while hunting may be another one.
The one in the tv room is different also.
When I practice with the sword, outside in the Yard, next to the woods, prior to sunrise, I have an entirely different pistol.