This one is surely a given, and has been all but confirmed by comments made by the cast. In the comic event Flashpoint, Barry saving his mother results in a dystopian version of the timeline. One where Aquaman and Wonder Woman are waging a war that is devastating the world, Superman is nowhere to be found and Bruce Wayne died as a young boy, while his father became the Batman. With the help of Thomas Wayne, Barry tries to get history back on track.
Obviously, this story can’t be adapted totally faithfully, due to the absence of all those heroes from the Arrowverse. However, there are enough alternate heroes running around for a version of Flashpoint to have an impact. Also, the comic features the Reverse-Flash as a major antagonist, and it would seem likely that the showrunners would look to bring back Eobard Thawne in a major way after the overall disappointment that was Zoom.