My thought process is literally "screw realism, do what looks pretty"
It might be the animator in me, but I feel like limiting yourself as a digital artist to what you can do/see in real life is such a disservice to the medium--the reason I'm pursuing animation as a career as opposed to live action film is because you aren't limited to what real life gives you! You can have characters with WILDLY different body types and sizes stand next to each other and look completely natural, you can do absolutely crazy things with perspective, ignore scene object continuity a lot easier than you can in live action film, and of course, in reference to this topic--you can get away with crazier, more dramatic/moody color and lighting without it feeling out of place.
Stylistically, my approach for the rest of my comic is going to be extremely light and color based. I'm aiming for a limited color palette look because my intention is that if I were to ever print my comic, I'd like people to flip through the pages and see a rainbow--and immediately know when a scene has changed, because the colors (and the mood) have shifted.
Here's a sneak peak at some upcoming panels in my comic that demonstrate what I'm talking about:
Here's some rough sketch concepts for an upcoming scene:
The header banner and overall color scheme for the city scenes of my comic:
And finally here are some layouts from an animatic I'm doing for my comic:
So yeah for me, I really like to ignore realism and really go for setting mood with color as a predominant focus. I really think how you approach it is going to vary based on what kind of story you want to tell and adversely, how you want your visuals to support the story you want to tell.