I could make a landscape painting on one layer easily enough - it wouldn't look anywhere close to my best work, but if I planned out the steps I was going to take, it'd be possible.
But there's no way I could recreate my usual style with a single layer. I have so many glowy lights, and stars, and gradiating colours... I need my layer modes, and I need to be able to segregate and alpha-lock colours in order to shade the way I like to.
I do tend to work with way fewer layers than a lot of artists, especially given mine is a sci-fi comic which requires fancy layer modes for glow effects. That stems from using Procreate with large canvas sizes, since that app limits layers relative to canvas size, DPI and RAM. I have more wiggle room now, since I upgraded to a new iPad, but I still have to watch my layer use carefully.