This idea has me intrigued, enough to bring me out of my shell and peak in...
I like the idea that you're up for building it with a group of people. Although I wonder Are you intending it to be a casual style rp or free style? 

As far as your thoughts:
I like the idea of single universe far better, but done in a way that maybe they all live in different parts of the same world and in some way get brought together in various ways, so maybe no all in the same neighborhood, but in the same world, for sure. 

Sandbox; yes and no... like there should be a little sandbox but there should also be structure, like an overall story or theme... or even same thing we're all trying to accomplish, thus giving us a reason to come together. 

OC's, I'd want to vote no in this particular setting, seeing as the idea is that you're meant to play someone from a CN show xD

Original CN shows would probably make things a little easier, should probably ask if there are specific shows that should be included, but I would of course vote for Powerpuff Girls, Ed, Edd and Eddy, Johnny Bravo and just about any of the old original shows. But I'm wondering what about adult swim shows at all? Like Family Guy or Robot Chicken... but then that might be opening a whole new can of worms... and I think that might overcomplicate things

I'm not sure about the comedic characters, I suppose it depends on what the storyline is and what you're trying to do...

- Evee