The idea of a world-hopping fantasy sci-fi adventure is kind of a no brainer.
Rather than making everything a zany comedy, actually play it straight as an action cartoon, like Dreamworks Voltron or Last Airbender. So the Castlevania world is a serious spooky horror world, he "Mega City" world is a sci-fi world full of robots, etc. Other than world leaders or certain important people, the worlds aren't aware of each other, and Princess Lana's father ruled over all of them to keep them separate.
Make the villains and creatures from each world distinct, so you could have episodes where Castlevania horrors are introduced to the Sci-Fi world, or a fantasy world is stripped for resources to make robots.
At this point, you could probably get away with stripping out the lisences and just making the game worlds unique pastiches; it'd give you the freedom to mix brands without dealing with the demands and limitations of lisence owners.
tl;dr kingdom hearts but good.