One thing that I've done is to base their mannerisms off somebody I know, or even an actor. That doesn't really help with getting character motivations correct, but I've found that if you start from the outward mannerisms, you can often discover some neat motivations for characters.
My current story has an elderly priest, who, for reasons that I've developed, is often grumpy. In my head, I started with Sean Connery from Finding Forrester, then took away the accent. Now, I don't know that I've come anywhere close to actually sounding like Sean Connery from that movie, but I do know that he sounds distinctly different from my main character, and from my other characters. I also have an antagonist character, who I really want to be obnoxious, so I brain-stormed my least favorite character from TV or movie, and came up with Todd Packer from 'The Office' or Louis Litt from 'Suits'. I kind of meshed those two guys together. So, any time I have these guys saying anything, I just imagine how these actors would do it.
