The most obvious difference between the show and the comic is the diversity. Most notably, Mark is biracial, and his mother is Korean American. Also, Amber is Black, Green Ghost and Shrinking Ray have been gender-swapped, and William is a proud gay man. Of course that last one happens in the comics, but more on that later.
When speaking on added diversity, Kirkman stated, "I think representation matters — not to get on a soapbox or anything — especially in the world of superheroes. You don't start getting non-white superheroes regularly until the '70s, and, even then, through the '80s, '90s, and 2000s, they're still somewhat rare. There's not a lot of these characters, to this day, that are different races. Anytime something can be changed to bring more representation into it, I think it's very important because there's a tremendous amount of people out there who don't see themselves in what they consume. But it's also very important because there's an audience hungry for this stuff; it actually benefits projects. So aside from being the right thing to do, it actually helps projects these days, which is a really great thing."