I try to stick to at least three changes. It's SO easy to get caught in the trap that your first design is the right one, but the truth is, it's rarely the one that'll stay right in the comic every panel - and if it's not consistent, then it's probably not working. That said, the second one sometimes is too complicated from other angles, making the third one very similar to it but with streamlined details, without having to "fix" the problems with the first attempt.
Here's an example with Elise. Rough sketch of what I want the outfit to be, first attempt and palette, second attempt with a nearly finalized design, then the final version.

And not pictured, but I got rid of the third row of buttons on her jacket because I constantly forgot it was there anyway. For minor characters, I rarely put this much work, but I try to at least have a first pass so the reference is the cleanest it can be.
For nonhuman characters it's way more involved, but I don't have any with a fully digital silhouette work. Here's Stormsever's process, where I was just sketching deer creatures nonstop until I found the right look.