The fact it has a fixed colour palette as well is fantastic, takes a lot of the guess work out of choosing the perfect colour, also means PICO-8 games have a shared look which is nice.
I'm working on a game at the moment which is inspired by old ZX Spectrum games, so sadly that rules PICO-8 out (different colour palettes), but otherwise those limitations make the whole thing really nice
Right out, the most interesting ones to me are WASM-4, because it seems to be one of the strictest and most minimal, and Pyxel, because it uses Python. Though to be fair I haven't actually tried either of them yet.
If you just want the "best" one (obviously very subjective, but its the easiest answer), try Pico8