Maybe I'm just too detached from the horror genre, but I can't think of a horror cartoon, past or present, that has really hit the scary mark (and no, Scooby-Doo doesn't count).
Resident Evil is the clear way to go here, with a notable backdrop revolving around the Umbrella Corporation giving the stage a broad platform to build upon. With Leon, Jill, Wesker, and other notable characters included, there's certainly no shortage of relationship conflicts. Of course, it still has to be a horror cartoon, so people need to die, and very gruesomely for that matter. But you can't just kill off Leon or Chris (at least not in the first season), so there'd need to be a bunch of Ensign Rickys to meet their grisly ends.
I think to keep things as realistic as possible, the show would have to be cinematic in quality. I know it's expensive to create those kind of visuals for an hour's worth of content every week, but just think of the viewership. Every horror junkie getting a weekly fix? There's your Zombie Apocalypse.
I think we're due for another space adventure cartoon series, at least something different than The Clone Wars.
Metroid would fit that bill perfectly. I wouldn't have thought so in the past, as all of Samus Aran's journeys have been relatively mute experiences with a stern focus on gameplay alone. Metroid: Other M broke the mold by bringing a story, some character development, and even the hierarchy of the Galactic Federation. The scripting and dialogue were not the best, and many of the relationships and plot points were extremely clichéd, but it did present a firm template to work with. There is a great chronology from our heroine's Zero Mission all the way up to her viral infection in Metroid Fusion, with plenty of space in between for new exploits.
Samus Aran has been a beloved character for decades, but one who's personal life has been left relatively untold. There is some respect in keeping her life private, so incredible care would be needed to make sure her identity isn't corrupted. But I'd like to see that risk taken nonetheless.
I knew I had to put a fighting game on the list; there are just so many characters in these games that need stories instead of just being fighting machines. But instead of picking a single universe, why not double the pleasure with a versus title? Marvel vs. Capcom was the first to come to mind, but those comic book superheroes have been given enough animated airtime as it is.
And then it hit me like a Lightning Screw Uppercut: Street Fighter X Tekken would be a perfect fit. Two great series, each with an impressive roster of characters. We have more character history with the Capcom clan, so it'd be nice to see Namco's group take center stage a good portion of the time.
Taking a feature straight from the game, maybe one of the overarching plots could be the acquisition of power-boosting gems. It'd be awesome to see Ryu and Kazuya battle it out week after week, and it might even be cool to have some cross universe-relationships. Ken and Nina perhaps?
Anyway, all I know is that the formula fits, and fans of both series would flock to their televisions for this action cartoon.