I’m no master of character design, but it is something I’ve tried hard to improve over the years.
Most of the time I have a mental image that I go with. With Marigold, for instance, I knew I wanted her to be a little heavy, and kind of mousy looking but still cute. With Lt. Potter in #2114, I imagined her being short, with dark hair and a slightly rounder face and nose than Faye (whose face is sort of the “default” in my head).
Occasionally l’ll pull ideas (aka STEAL BLATANTLY) from other things. Dale’s design is clearly a nod to Spike from Cowboy Bebop. Momo is a mishmash of all sorts of “moe” stuff. So, uh, anime. Yes.
Other times I just make something up off the top of my head. Occasionally a character design will appear in my sketchbook and lurk there for a long time before it ever works its way into the comic. I was drawing Hannelore for like two years before I ever knew who she was or whether she’d show up in the comic.