Lots of good stuff in this thread already, but I'll throw my two cents in as well.
1.) Variation is key
Any comic that features more than one character should have more than one facial shape, more than one body type, and more than one type of behaviour. Don't get stuck drawing the same faces bodies just because that's what you feel comfortable with - challenging ourselves is how we learn. Draw short people and tall people, thin people and fat people, people with big noses and people with small noses. Draw people who walk with straight backs and their heads held high - draw people who slouch; draw people who shuffle around.
Example from my own comic:
Leaving aside the contrast in their body shapes and faces (being adult and child, Masahiro and Akane are bound to look very different), I'll use them to talk about movement patterns. Akane's a curious kid, so she tends to walk around staring at things, peeking around corners, never following the path if she can climb over stuff
beside the path instead - she's got a very
open sort of body language. Masahiro on the other hand, is a more troubled person, and tends to walk around with his shoulders drawn up, arms close to his body to keep from getting into the personal spaces of others - and to keep those others from getting into his. When he's just sitting around relaxing (... for given a value of "relaxing"; he's pretty tense) he tends to slump
forward, kind of curling in on himself. He's got a very
closed sort of body language.
So, even if they were the same size and shape, they would move differently.
2. a) Functionality
Since these are comic-characters were talking about - you're going to be drawing them a LOT of times. You're going to be drawing them from all sorts of angles, in lots of settings, and if you're drawing it in colour - in lots of various lighting situations. You're going to have to consider their designs from all angles, to make sure you know how to draw it, and to make sure it works from every angle. That awesome tattoo on their arm might look really cool from the front - but when you have to draw them from the back and you realise it doesn't work from that angle.
Then, of course, you have to make sure it's a design that's a.) complex enough to stand out, but also b.) simple enough that you can remember all the details you've put into it. That amazing swirling pattern might seem like a good idea in the design sketch, but that's before you have to draw it in 200 different panels.
2.b)
Unless you're drawing a comic about fashion design or fashionistas in general, it's unlikely that people are going to be walking around in clothes they can't sit down in. The functionality-issue isn't just for you as an artist - it's for the characters as well. What they can and will wear will depend on their personality, their daily activities, and what sort of clothes would be available to them. Someone who works outdoors will be wearing practical, hardwearing clothing. Someone who likes sitting around inside reading will be wearing something suitable for that. Someone who has to run around a lot will probably be wearing sneakers - if your setting allows for sneakers.
Again, to use myself as an example - Masahiro's clothes are ragged and torn and kind of make-shift stitched together because those clothes are all he has available. He has to make do with them, because he can't just turn around and get new ones when the old ones start looking worn out.
3.) Visual keywords
Colour-schemes, patterns, hair cuts, etc. Stuff that will make your readers know that the character is THE specific character, even at a distance or from weird angles. Really think about the colours you choose for their clothing, or the way you make them dress, or how they cut their hair. Use that colour scheme to make them stand out from everyone else - or connect them, specifically, to someone or something else in the comic. Uniforms, for example - they look like the characters wearing them are connected, even if their body shapes and their mannerisms are entirely different.
If I draw a crowd of people, my readers will be able to pick Masahiro out of it, because he'll be the one walking around in a white-yellow-grey outfit, and he'll probably be the only one in the crowd to do so. Likewise, they'll know that the character whose shoulder+sleeve are barely in the frame belong to Akane, because it's blue-beige. And so on.