I think it's less about what type of story you're writing and more about what kind of a mood you want to create in your work.
For example, both Up! and Maus are stories with plenty of heart-wrenching/serious moments, but they're done in very simplistic, cartoony styles. In both cases, it was entirely on purpose, and they would read like different stories if they were done in a more realistic style (or, in the case of Up!, were live-action movies... forgoing some of the more cartoony elements).
Likewise, comedic, light-hearted stories can be told with more realistic characters and they will be read entirely different from a comedic, light-hearted story done in a super-exaggerated, cartoony style.
So... It's kind of something you need to decide when it comes to your story - which will serve as the best vehicle to deliver your ideas.
(I've given this a lot of thought, hah. Sort of faced a similar problem myself, though I've pretty much decided on what I want to use)