Supergirl (Melissa Benoist) has the most to lose in Arrowverse crossever Crisis On Infinite Earths, because she could be forced to watch multiple versions of her loved ones die. This year's crossover promises to be the biggest ever, spanning Supergirl, Batwoman, The Flash, Arrow, and DC's Legends of Tomorrow. The superheroes will do battle with a cosmic being called the Anti-Monitor (LaMonica Garrett) who wants to wipe out the Multiverse.
Crisis On Infinite Earths will honor past versions of DC's superheroes, especially previous TV shows and movies about Superman. Not only will Brandon Routh once again play the Man of Steel - specifically an older Kingdom Come Superman - but Tom Welling and Erica Durance, the Superman and Lois Lane from Smallville, will also be part of the Crisis. In addition, Lynda Carter might also reprise her role as Wonder Woman from the 1970s TV show. On top of all that, Supergirl's Superman (Tyler Hoechlin) and Lois Lane (Elizabeth Tulloch) will also return for the Crisis. The alternate reality Earths of Kingdom Come Superman and Smallville are threatened by the Crisis, along with the rest of the 53 known worlds of the Arrowverse's Multiverse, including Supergirl's Earth-38.
But for Supergirl, all of these Super guest stars are extra personal because they're doppelgangers of her cousin Superman and other people dear to her. Three Supermen in the Crisis means there are three different versions of her cousin Clark and, unless fans are somehow led to believe otherwise, none of the three Supermen look alike, which will be very bizarre for Kara Danvers to process. Further, Erica Durance already appears in Supergirl as Alura, Kara's Kryptonian mother, which means that if Kara meets Smallville's Lois, she'll be incredibly confused as to why the Daily Planet reporter is a doppelganger for her mom. And if Lynda Carter does return as Wonder Woman, that means the Amazon is the spitting image of Supergirl's Olivia Marsdin, the Durlan who was President of the United States on Earth-38!
Of course, Supergirl has dealt with exact doubles before: Kara fought Bizarro Supergirl in Supergirl season 1 and she wrapped up Supergirl season 4 by defeating Red Daughter, the Russian duplicate of the Girl of Steel manipulated by Lex Luthor (Jon Cryer). (Meanwhile, Michael Rosenbaum will not reprise his role as Smallville's Lex Luthor in the Crisis, which at least eliminates that headache for Supergirl.) Evil doppelgangers have been a key element in past Arrowverse crossovers: in Elseworlds, John Deegan (Jeremy Davies) used the Book of Destiny to transform himself into the Black Suit Superman while in 2017's Crisis On Earth-X crossover, Supergirl and Green Arrow (Stephen Amell) faced their Nazi doppelgangers Overgirl and Dark Archer. But the Crisis promises to be different and potentially even more traumatic for Kara.
The comic book Crisis On Infinite Earths melded the numerous alternate realities of the DC Universe into one Prime Earth, which resulted in many continuities being wiped from existence. The Arrowverse's Crisis could do the same; while a potential benefit would be Supergirl's Earth-38 and Black Lightning's Earth becoming unified with Arrow and The Flash's Earth-One, it could also mean the destruction of the other Earths - like Kingdom Come Superman's and Smallville's.
The grim possibility is that the non-Arrowverse worlds may not survive the Crisis and this means that Supergirl could be forced to watch the alternate versions of her cousin Clark, her mom Alura, and maybe even President Marsden perish forever. Supergirl herself died in the comic book Crisis and while that might not come to pass in the Arrowverse, Kara could not only lose her cousin Clark (the Tyler Hoechlin version) to the catastrophe - indeed, every version of Superman might die in the Crisis.
The stakes are truly Multiversal in Crisis On Infinite Earths and the Arrowverse will likely be permanently altered. But because so much of the Crisis is a celebration of Superman's movie and TV history, it could all lead to an ultimate tragedy for Supergirl; Kara Zor-El personally has the most to lose and she could be emotionally scarred forever.