Ah no one picked up the Doomguy joke, oh well. It is kind of a joke about "what about the settings that don't even make sense?" Doomguy is a regular solider who fought off (and then took the fight to) all the forces of hell. Pit of Kid Icarus canonically has infinite lives/retries so can never be killed permanently. And of course there are the extensive comic book stories with absurd beings and powers yet somehow it never actually effects daily life on earth.

Thinking about the interactions between settings is fun though, but I like the weird ones for this. Like Dark Ocean which is a multiverse separated by an endless night filed with monsters and rock. The rocks (and the fact there is air here) stop most spaceships and even if you can get ground forces deployed the monsters will probably tare your apart before you reach any of the settled areas. And even if you start at one getting to the next is getting to the next is going to be a chore and the locals... well they are prepared. I mean they started breeding 10 headed dragons because the old 6 headed dragon breeds just weren't doing enough damage. Also the incredibly terrifying warriors these things are designed to fight tend to also be artists and politicians who are comfortable working on a centuries long time scale. So forget military might, against most other settings they will probably just force a stand-still and then assimilate the attacking universe.