Ouch, that's actually kind of a tough question. Ooo has an interesting and detailed backstory that does a good job of explaining its loony tunes logic. Equestria is a little less detailed, but what's there is an interesting variation of traditional fantasy tropes that you don't often see used together.
Both settings have interesting creatures, Ooo's can be more hit or miss for me, with some places looking more like they just wanted to add something bizarre and stupid, or trying to appeal to stoner humor. Equestria's creatures are more consistent, but also a little less out there, since they pretty much all draw from various real world mythologies, even the more bizarre characters like ahuizotl are adaptations of actual mythological creatures, which for someone like me, who loves traditional mythology, is more interesting than Ooo's grab bag of candy people, amorphous blobs, and talking lemons.
The history is more detailed with Ooo, and the whole post-apocalyptic thing gives it a dissonant tragedy to offset the often whimsical creatures and setting. Equestria's history is a little more traditional fantasy faire. Ooo's is more interesting to me in this case, simply because they do more with it.
In regards to present setting, both are interesting in their own ways, Ooo for its weird almost dreamlike qualities with its somber background, and Equestria with its fantasy tropes subverted and given a new spin. For Equestria, they take a lot of cliche fantasy tropes and put them in a world that fantasy rarely utilizes well. The first point being, you've got a fantasy setting with nary a human, dwarf, or elf in sight, allowing the whole setting to focus on more exotic creatures without worrying about the narrative being hijacked by generic human audience insert character A. Equestria also nicely sidesteps the technological stagnation issue that infests a lot of settings, with actual steam trains and other technology, Equestria isn't stuck in an eternal medieval dark age like so many other fantasy settings, which gives the whole setting a really nice smattering of industrial revolution and late 19th early 20th century technological flair.
In the end, I'm just barely voting for Equestria on this one, more because I really enjoy the fantasy approach and interpretation of traditional fantasy creatures into a world that isn't dominated by the same old humans, short humans, and humans with pointy ears, that infests so much of the fantasy genre. I like them both, but Equestria is a little more interesting to me as a whole.
