In a nutshell, just serious enough that I can maintain the illusion to myself that, should I ever write out one of my campaigns as a novel, movie, or TV show, it would be worth watching as a drama/action/not-comedy.
In other words, the story line is reasonably serious, with tension-breaking humor and the like totally acceptable. But... we're all friends (I've known a couple of the players for close to 30 years) and we're together to have fun. So, it probably plays more like seasons 6+ of Supernatural, where you know the cast and crew is there just because they're having a good time, Scooby Doo episodes and all. But, I hope you can still see the conceptual foundation that was present in seasons 1-5.
The only explicit rules I have are:
* No joke names. They're just too hard to shove behind a curtain when we do want a serious scene. Like having one actor in Die Hard who thinks he's doing Airplane.
* No gender bending. I don't have any theoretic issue with this. I've just exhausted my limit of bad experiences and have no interest in putting my hand on the stove, again. I'd probably bend or even toss this one, at this point. But, it came about when I was younger and had a looser membership in my group. I was always shocked at which guys were latent misogynists with a leather fetish -- something I really didn't want to know.
* No Wuxia or similar tropes. For most genres, I have a cap on my ability to suspend disbelief for "mortals". 1980s action movie physics is fine. Having some mages around is fine. Having Conan do a flying, head-first, horizontal spin across a 15 foot gap while exchanging sword play with the BBEG, not so much. Steampunk devices generally fall into this one, too, as they're too improbable. If we're playing a supers game or something similarly high-powered or magical (Sons of Ether, for example), it's a different story, but those aren't about "mortals".