DC/Marvel/Dark Horse/Image Comics Crossover
Each player would be a member of a team, probably brand new, that is there to protect time and space (think Legend of Tomorrow but with the other comics mixed in). The game would take place in chapters, with each chapter dedicated to a specific event, like Marvel’s Fear Itself and DC’s War of Light. And since it is a crossover, you’ll see DC characters in Marvel events and Marvel characters in DC events, etc.
Magic: the Gathering
I have run a short version of this before and have proposed a larger scale version that never came to fruition but am willing to revisit the idea again. Each player would play a Planeswalker and would travel the multiverse learning new spells and making new allies and solving all types of problems. This is one of those setting with a lot of freedom for the players. Don’t like fighting eldritch horrors? Fancy a more political game? It is as simple as just walking from one plane to another. Gather enough interest and I might even start doing custom planes and custom card contests!
Each player would take on some sort of investigator or hunter that specializes in the supernatural/paranormal, traveling around the country (or world) solving cases and killing evil things. Hunting vampires and werewolves, helping the dead to pass on, etc. I might even allow some minor things for the hunter and investigators, such as being a psychic or medium.
All of the players are survivors of a horrible accident and are trying to survive until they are rescued or until they can escape. Someone, or something, is trying to kill the players, stalking them in the night. Cannibals, wild animals, zombies, mutants, etc. It could be an empty island, abandoned city, or something else entirely. The goal here would simply be to survive as long as possible. This is one of those games where we can all post, or where I am the only one that posts but what happens is based on the voting of those participating (I think there was a rather successful Skyrim RP with this idea)., whichever you all would prefer.