In descending order of importance
for HD handgun:
1) Price. Can I afford the thing? I'm not going to spend $2000 on a custom 1911 or somesuch. On this note, I don't own any guns that cost over $600.
2) Size. Can I hold and manuver it properly? NAA .22s and Desert Eagle .50s need not apply... things around the Beretta 92FS or 5" 1911 size are the norm.
3) Caliber. Will it stop them/it if I do my part? At least a 9mm is preferred, and nothing over a 10ga.
4) Controls. Does operating it feel natural in case I panic? Any gun that doesn't release the mag by a button near the strong hand's thumb--like a Walther P99 or HK USP, or any European gun that clamps onto the bottom of the mag--is not preferred. No revolvers for me, only because I've never fired one and, because of this, wouldn't be comfortable using one to defend my home.
5) Capacity. The more, the better. However, I'd rather have five shots of .44 mag than 30 of .22lr.
6) Reliability. Will it work when I need it?
7) Availability of spare parts. If it breaks, can I fix it?
8) Cool factor. What movies was it used in? Are they movies I like?
(Seriously, though... I'm trying to be honest here) I'll pick a Beretta 87 Target over a Ruger Mk. III because I love the movie Equilibrium.
9) SA/ DA-SA/ DAO/ Pump/ Semi/ etc. I usually go with DA-SA or DAO whenever I can, based solely on preference. I just like 'em better. *shrug*
That's just me, though...