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Star Trek / Mass Effect
The parallels between these two series are fairly clear, and it's high time we though about having the Enterprise and Normandy meet up. After all, we've never really gotten a Star Trek game worthy of the name, and the Mass Effect series has the blueprint for making it great. What if the Reapers were assimilated by the Borg, which then set its sights on humanity? You could have Federation / Council alliances, plenty of iconic characters from both universes, and you'd get to see a fight between Wrex and Worf (of course, their respective captains would stop the fight before either one was killed). How could it get any better than that?