I think 12-bit RGB (4096 colors) is good niche, having the advantage of 3-digit hex codes (so you have something like #ac3 (#aacc33 where unsupported) rather than something that looks like #ff6b35), which if not more convenient is certainly a lot more of an obvious gamut.

I haven’t done pixel art in a while though (my results were mixed, and I don’t think I was aware of 3-digit hex) and even back then I was already at the point where I was creating models to replace ugly textures. So I’m looking to avoid texturing even more now.