I guess it could be done, although I only speak with the experience of making a graphical/text hack (nothing that can be called advance hacking) years ago that I never released because of how silly it was.
I changed characters, enemies, items and bosses to a random mix of Youtube Poop things, like Zelda C-DI/Hotel Mario, and other weird things that I happened to see back then when YTP were relevant as a joke between some friends and me.
The playable characters were The King, CD-I Link, Morshu and Gwonam. The bosses were a taken from different parts of the YTP universe, CD-I Ganon being the substitute for Wart, so I think Bowser could fit in it.
What I'm trying to say is that as far as graphics go, I remember the game being easy to work with, with the exception of some bosses like the snake one, which I ended up doing something so stupid I don't even want to name it, so it's not much of a problem.
The change in gameplay for some enemies on the other hand...
Here's a random screenshot:
Here, The King (Which is Mario's substitute) fights a reworked Birdo: A Fake CD-I Mario with a toaster!
Toasters toast toast, so that's what he shoots. When you defeat him his fake moustache goes flying.
And here is...
A...Nigel Thornberry...bird...thing. And Morshu (Toad's substitution).
The snakes in world 2 were changed to Waluigi-esque stick figures.
Man, this thing brings memories. It was my first hack ever. I learnt how to do graphical changes and text changes through it.