The Comics: One of the most recent DC Comics events that can influence the crossover is 2013-2014’s Forever Evil by Geoff Johns and David Finch. The plot of this multi-issue story arc revolves mainly on the DC Universe’s villains. The Crime Syndicate decide to go on a massive prison break all over the planet letting villains free from any major prisons out there. This happens while the Justice League is out of commission in a destroyed Watchtower, so minor-scope heroes have to face this Earth-3 threat. Mayhem ensues, and certain villains (led by Lex Luthor) take it upon themselves to help out and be temporary heroes to fight this onslaught of villains.
The Crossover: We don’t have the Justice League, but we do have access to the multiverse. Earth-3 is currently manned by Jesse Quick and we have yet to be introduced to any sort of Crime Syndicate. Introduce villainous versions of Barry Allen and Supergirl led by a (worse) Green Arrow and you got CW/DC’s version of this Syndicate. Following the comic book storyline, this supervillain team could tag team Jesse Quick and, after taking Earth-3 by storm, they can move over to Earth-38. This would be the point where Supergirl would call on Team Flash, Team Arrow, and the Legends to help out. Considering Kara’s Earth is undoubtedly awash with alien-filled prisons, it would allow for a second “Heroes vs Aliens” clash.