Late to the party here but here's my two cents.
From years of drawing and creating comics, the best piece of advice I can give you is to work on your style and features you want to include in each characters to set them apart. Let me show you examples through my characters.
I spent a while thinking on how to design my characters. Since my style leans more toward realism I studied many face types from eye shape, nose shape, down to common features based on race and ethnicity. Same with body types. I often will join live drawing classes that employs diverse range of models to understand different body types and study them live.
I also saved a lot of references of said examples in both my computer and sketch books as references. Basically, references are extremely important to me. After that I just adjust to my own style.
On top of that I also consider other features when designing characters. For example, based on their personalities I will adjust their facial features in this case their eyes. Eli (mohawk guy) has hooded eyes because I want those bedroom eyes since he's a flirty type. Hotaru (long hair) has upward slanted eyes with smaller pupils since he's more serious and stern (aside from him having Asian ancestry). And so on and so forth.
Outside of facial features, I also consider their clothing style to express their personalities. Eli is a metal head so he wears a battle vest. Hotaru dresses more simply because he's more introverted but he also likes tailored pieces because he likes to look presentable. I also include identifying secondary features like accessories and tattoos. Eli wears a necklace that has a significant importance to him. Hotaru has a few tattoos (that you can't see here) because he's interested in body modification on top of doing it as an act of rebellion towards his overly strict mother. These little details are important to communicate to readers what these characters are all about. Then lastly, I also consider their mannerisms. Eli is brash and vulgar so he cusses a lot and more expressive in his movements. Hotaru, meanwhile, almost never cuss so when he does you know he means business. He's also more eloquent since he's more mature and considerate.
I hope this helps out since there are already other great advices in this thread.