A favorite is hard for me, and this question has come up many times. I don't really have a best, or a preferred perk. It changes every time I play. Sometimes you want to blast specimens with a shotgun, sometimes you want to light them on fire. *shrug*
If I absolutely had to choose, just a single one, it would be sharpshooter - simply because I integrate sharpshooter weapons into many of my loadouts for other perks like demo, firebug, zerker, medic, etc. Would prefer an unperked handcannon over an unperked shotgun due to being able to use it more precisely.