After years of development, showcased much better in Zack Snyder's Justice League.
Very few details about the story have been revealed other than it is a new story inspired by other comic storylines. And currently, there is no official confirmation as to who the main villain is. So who would be powerful enough to need the combined forces of The Flash, multiple versions of Batman, and Supergirl?
Gorilla Grodd
One of the Flash's most iconic foes, Gorilla Grodd is a genius who could create a way to use inter-dimensional transit. However, Grodd in the comics is not the kind of character that wants to destroy the Multiverse.
Still, the DC Extended Universe has already made several unique changes to characters. Perhaps Grodd's aspirations are a bit bigger this time around; instead of wiping one Earth of all humanity, he wants to rid all worlds of them.
Daniel West
The second Reverse-Flash, Daniel West is Iris West's brother who wants nothing more than to murder his own father. With the DCEU, his madness could lead to an even more complex plot involving him traveling the Multiverse and creating chaos.
Unfortunately, Daniel West in the first Flash movie would be a bit of a rush since Kiersey Clemons' Iris herself has had one scene in the DCEU. It would be better to save him for a future sequel but the involvement of the character is still a probability.
Black Flash
Another monstrous speedster, Black Flash is the grim reaper of speedsters. A way to involve him is by having Barry living on borrowed time as the Multiverse is being destroyed. As a result, Barry is constantly being chased throughout the film.
Black Flash would be a perfect way to add tension with Barry trying to keep himself from fading away and outrace the creature. As a bonus, Black Flash could provide horror for the film which would be no problem for the director since he previously made Stephen King's IT.
Doctor Alchemy
Using the Philosopher's Stone, Doctor Alchemy has the ability to transmute any element. It's not exactly far-fetched to think Alchemy discovers the way to transmute elements into a way to travel from universe to universe.
Easy motivation: he is beaten by Barry and as revenge and wants to eliminate him from the Multiverse. Perhaps he s forces with other villains including The Rogues to get the job done.
Vibe
Francisco Ramon is typically depicted as a hero but the DCEU could take things in a different direction. Perhaps this Vibe gets his powers when Darkseid arrives in the Knightmare future shown in Zack Snyder's Justice League. As a result, he becomes so determined to prevent Darkseid and an evil Superman.
Vibe begins to traverse the Multiverse and he erases the Justice League. Trying to stop that future for every Earth but as a result, he is causing more deaths than Darkseid. Vibe could be a more tragic anti-hero whom Flash has to stop by trying to make him into a hero.
Mirror Master
The character's main abilities are all about traveling through a mirror dimension. Alternate universes are in a way, a mirror of other worlds so Mirror Master discovering a way to traverse the multiverse is not far-fetched. With the DCEU, Mirror Master could be altered to be given a more complex story than an evil assassin.
CW's Arrowverse is a perfect example of how much Mirror Master can be changed into a more powerful villain. In that universe, the name of Mirror Master is also used by multiple people.
Captain Cold
Obviously, Captain Cold is one of Barry Allen's greatest foes. He often leads a group of Flash's enemies called The Rogues. With Captain Cold as the main villain, the Rogues could be working together to kill The Flash in all worlds including the DCEU.
This would allow for audiences to see that he is not a Mr. Freeze rip-off. He's an intelligent criminal and strategist who has a moral code. He never hearts civilians unless absolutely necessary: never to be cruel.
Prometheus
The best way to describe Prometheus is an anti-Batman. A psychotic genius who witnessed his parents' murder by the police. He now seeks to eradicate all forms of a justice system. The moniker of Prometheus has been worn by many people across DC history so the DCEU could do anything with the character.
Perhaps he becomes determined to destroy superheroes across the Multiverse or even destroy the Multiverse itself. The character is crazy enough and he has killed and wounded many superheroes before. This makes him fit for the DCEU considering how dark some of their villains can be.
Reverse-Flash
The most obvious and likely villain is the Reverse-Flash AKA Eobard Thawne. Batman has Joker, Superman has Lex Luthor, and Barry Allen has the Reverse-Flash. Reverse-Flash's entire scheme is to destroy Barry Allen physically, emotionally, and psychologically.
Reverse-Flash also wants to be the one true speedster. He can't have that with a Multiverse of speedsters out there and likely alternate versions of Barry. Thawne is crazy enough to attempt a killing spree that big and likely uses other villains as pawns. The director and his wife/producer even teased Thawne on social media.
Knightmare Flash
Reverse-Flash is a little too obvious, so why not trick the audience? An evil speedster creating havoc could lead the viewers to speculate Eobard Thawne. In the climax, it is revealed to be Barry Allen himself from the Knightmare future gone mad from all the death of those he cares about.
Think about it: what happened to Knightmare Flash after he warned Bruce Wayne in Batman V Superman: Dawn Of Justice? It's never shown. Perhaps he discovered the Multiverse and the many alternate realities where Darkseid wins, thus turning him into a villain.