This is an interesting question, and one that I've actually been thinking about just recently. The main characters of my comic (which I'm still in the process of making) are loosely based on my closest friends in real life (and naturally, I've just kept them the same gender/sex), with the main character being based off of myself. Originally, he was just male because I'm male, but recently I've developed a desire to turn him into a female character, for no other good reason than "I simply want to."
The one thing that was (is?) holding me back from going through with this is the fear that my comic will fall under judgment for having this dynamic. For example, because I am writing a female main character, while being a male, I fear that I will come across as assuming that men and women are exactly alike, or I just don't know how women work. However, I don't want to appear like I think being a man or a woman affects your personality, and what you like or don't like (because that's just silly). Since my comic will be centered around interactions (it's basically a bunch of opinions with faces walking around, haha), I don't think it would matter too much if my main character was male, female, or otherwise, as long as they had a defined...character, I guess.
Sorry for rambling (I do that from now and again), but I appreciate getting to converse about people's different thoughts on this topic! Thank you for bringing it up, and I wish your journey with your webcomic well (I'll be following it from now on, it looks like a very fun and interesting story)! 