Billy and Mandy, even when attached to Evil con Carne in "Grim and Evil" would have been great, and a runaway hit, except for one prominent feature:
He was just a little TOO obnoxious and annoying to be tolerable. Even the voice, clearly being done by an adult trying to sound as stupid and shouty as possible.
Having a somewhat obnoxious or "annoying" character to take the piss out of horror and dark elements is all in good fun, but there are limits. Like, it was really hard to find Billy endearing instead of outright aggravating, and when your overarching show themes are supposed to be references and jokes regarding mythical, occult, and supernatural things, your target audience loses interest when everything is constantly deflated by some retarded kid who always seems to grind plot/character progression to a halt because of retard shenanigans and toilet humor.
It's like they wanted the pre-teen, sci-fi/fantasy fan audience, but also 7-10 year old normalfag kids. I always felt like the show had lots of great production and passion put into it, but was forever at odds with itself, and just seemed somewhat awkward unless it could really settle itself into a niche, which it never did.