When there is genuine flexibility of choice I think of the personality I want. Sometimes stolen from a book or movie, sometimes my own invention. The skills/class/whatever are chosen around that idea. I always pick something with which I can identify, or see an element of myself in, no matter how small. No disgustingly happy, hopelessly naive Aeris Gainsborough types allowed.
In Fallout 3 my character was basically Jayne Cobb. Sure, I'll help ya, but I *will* get paid, and I'll sex up your sister while I'm at it.
In Mass Effect I wanted to play a hard-line military man, someone who had a job to do and was going to get it done regardless of anyone else's opinion on the matter. Couldn't play the game due to technical issues but this was my intent.
I used to play the disgustingly good paladin type in every game but this is much more fun.
In games whose choices are simple good vs evil I always play the good guy -- KOTOR, inFamous, etc. (Yes I know KOTOR offered a spectrum of choice but the Force powers locked you in to one extreme or the other). I save bad guy for replays.