How about… nope, been done. What if… nope seen it. Seriously, are they asking RPG genre or just a broader genre they want created? Zombie romance – been done. Cthulhu everything – been done. Probably a lunch box for it. Teenage girls fighting horrific monsters – seen it. I am not the most original person in the world. What I do well is to take existing genres and make them feel new. I am proud of that. I do not wake up in the morning thinking of a new mash up like;
The world needs an Anne Rice styled vampire RPG mixed with the dystopian all-spying world that is 1984. Or even better Paranoia where the computer is replaced by Lestat…
There is a little bit of blood oozing from my right ear just because of the stress of coming up with that mash up.
What is good for a mash up?
Collaboration is great for a mash up. It is also awful for it! I have sat down with several groups with FATE to come up with something interesting and seen the best and worst cross the table. The first FATE Core session I tried to have with a group came up with the worst setting I could possibly imagine. Here are the index cards to prove it!

The setting was an asteroid filled with miners that had been abandoned by the company. The ships on the asteroid destroyed by the Vlaag’s (giant scarab beetles) who were now harvesting the remaining survivors for food. There was a cult that sprang up (the Seekers) and a horrid apocalyptic leadership group who had nefarious ideals in play.
Learned a lot about a mash up
Building that setting was loads of fun but it never got played. We put it away for a day when all the players for Pathfinder did not show up. It was an interesting evening though. I was with a group of players that had never played a story based RPG before. They had their eyes opened and I learned a lot about myself. Mainly that I am useless at making mash ups!
So I have no clear and present answer to this question. I will be awed by many of the answers that pop up because of it. I will wonder why I never thought of that before. The answer is of course that I am not terribly creative. I am inventive and that is a whole different thing. Keep rolling!