I would create various mods in one instance to make the enemies into pokemon and make a sub game out of it in some way.
Another would be to create a custom character with custom abilities based on a point system so as not to make an OP character. Think create a fighter and fighting styles.
Maybe make a more modern playable character base where you are soldiers with guns and u are transported into the demon realm and u have to fight your way back. ARPG DOOMish/haloish
Make it a halo game. Various human heroes/elites unlockable super characters, brutes etc… vs varying halo enemies, covs and Prometheus, as well as flood. Leave in the demons.
Hell while we are at it, i always enjoyed the legacy of kain games why not make it from that too. Health slowly drains u have to drink the blood of your enemies for strength and power. Soul reaver weapons and supernatural abilities.
The list goes on. Clash the warcraft/starcraft characters with diablo. Everyone gets sucked into the diablo world and each faction has to find their way to their own realm, a multiverse theme.