It depends on what you're doing, I guess. A comedy would probably be alright, but a gritty drama might not sit as well.
If you still want to have parts of your friends in the comic what you could do is caricature them. Pick a couple key traits or quirks that really stand out and make a character with that. Let's say you have a friend named Billy, who is kinda shy and wears headphones all the time. Those are just two little parts to Billy, but it'd be enough to give you a place to start for a character, who would then have his own goals, plot line, etc. There'd be enough that Billy is "in" the comic, but not so much that he's in the comic, y'know?
As for my own characters, usually it starts with a dumb idea or some name/object/occupation that I find interesting. There are also plot function characters, who are there because the story needs them to be. For those ones, the issue is finding that quirk or spark that makes them exciting to write.