I think Slider_Quinn21 is really onto something with the idea that the Reverse Flash's alterations to history resulted in the ARROWverse lacking Supergirl and Superman, but I think the idea of the Reverse Flash doing one thing in SUPERGIRL's continuity and something else in the ARROWverse is too complicated for a television show.
I think a simpler route might be preferable while still using Slider_Quinn21's ideas: specifically, SUPERGIRL is the original timeline without Thawne's interference or any changes in history wrought by Thawne and the Flash's battles across time. But when Thawne killed Nora Allen and assumed Harrison Wells' identity, he also used his knowledge of the future to (a) divert Kara's pod into the sun to kill her (b) depower Clark Kent and (c) also eliminate or interfere with the origin stories of any metahumans who might have interfered with his plans.
In addition, Thawne's drive to build the particle accelerator at an earlier point caused certain people to meet resulting in specific individuals being born -- Caitlin and Cisco -- whereas the original Harrison Wells built the particle accelerator much, much later in life (and Thawne stole his identity to build it "sooner"). That's why Caitlin and Cisco exist on Earth 2 (where Harry built the accelerator with the same drive as his Earth 1 impostor) but don't exist in SUPERGIRL's universe (where the real Wells is building the accelerator at a slower pace).
This would be a way to deepen Thawne's evil; he didn't just alter Barry's life into an existence where his father was in jail for his mother's murder -- he created a world without Superman and Supergirl. Meanwhile, the original timeline carries on as a separate, parallel track in SUPERGIRL (which is a timeline where Barry was much older when he became the Flash, so old he looked more like John Wesley Shipp than Grant Gustin).
When Eddie killed himself and erased Thawne's existence, everyone's memories of Thawne were still intact, Barry's mother was still dead, and the paradoxical nature of the timeline resulted in the black hole and the portals to Earth 2. And now Barry has gone back and stopped Thawne from changing history when the universe seemed to crack from Thawne's forcible removal from the relative present day -- which could mean that the FLASHPOINT reality we'll see in the Season 3 reality is a mixture of the post-erasure timeline (Cisco and Caitlin) along with the original timeline (Supergirl and Superman).
So maybe by the end of FLASHPOINT, the SUPERGIRL and ARROWverse timelines are restored into one, but some of the Thawne-created scar tissue (all the ARROWverse characters) remain intermixed with the present day SUPERGIRL timeline.
Actually, this may be more complicated than Slider_Quinn21's approach. How to distill it --
THAWNE: "This world isn't real, FLASH!"
BARRY: "This is the world we'd have if you'd never touched it -- "
THAWNE: "This deranged wonderland's a mismash of overlapping timelines! You think your parents were the only people I took out of the equation? I didn't just make you the Flash, I made you *my* Flash, I couldn't have any other influences on poor little Barry Allen, so desperate for a mentor. So I had to take away anyone who might have interfered -- a certain Kryptonian had to lose his powers, a little pod in space had to be diverted into the sun -- "
BARRY: "Kara -- there's no Kara on my world because you killed her -- "
THAWNE: "And there was no Cisco or Caitlin until I made them the same way I made you! If they're here, then this isn't the world without me, Flash, this is every bit the world I made except you've let it all go mad -- "
I dunno. It's a bit much. But while this unfolds on THE FLASH, I would have Winn over on SUPERGIRL inexplicably mention that he once met Felicity briefly, Cat would mention Oliver as a one night fling and in ARROW, the Martian Manhunter should show up in one of Oliver's flashbacks. Then FLASHPOINT ends and we realize the ARROW and SUPERGIRL episodes took place after the FLASHPOINT conclusion merged the timelines.
Oh, I love how Grant Gustin thinks that Barry would be head over heels in love with Kara Danvers while Melissa Benoist is of the opinion that Kara is too similar to Barry for there to be effective chemistry. I think that the characters should have exactly the same viewpoints with Barry smitten with a Supergirl who thinks of him as a buddy.