It may be a bit biased, since I'm a fan of all 4 of these guys, but the 4 that had it the worst were Rex, Spring Man, Octoling and Shantae. I know some might argue for Isaac, Shadow and Skull Kid, but they were previously ATs and were likely going to reprise those roles (as they did). Not saying that they didn't get screwed over (they did get screwed pretty badly), but their deconfirmation was far more likely than Rex, Spring Man, Octoling and Shantae.
Rex, Spring Man and Octoling, as many others have stated, were killed off before they even had the chance to prove themselves. We all thought these guys were gonna be locks for DLC as promotional characters, only for them to get deconfirmed with the rest of the fan-favorites. Spring Man is an AT, Rex is a Mii Costume, and Octoling is a Spirit (which, knowing that DLC was planned ahead of time, DO deconfirm fighters), along with the fact that there will be no echoes for DLC.
It's even worse for Rex and Spring Man. For Rex, there's likely to be another Xenoblade Game by the time development begins for the Smash 6/7 (if there is one), so whoever the Xenoblade 3 protagonist is is likely to take the slot that would've gone to Rex, so SSBU DLC was his only chance. ARMS didn't become as popular as Nintendo had hoped, so I doubt ARMS is going to be coming back any time soon, leaving the Smash team with no reason to touch it again.
Now for the unpopular opinion: Shantae. As I said before, Spirits do deconfirm fighters, since the DLC was planned ahead of time. But what makes Shantae's deconfirmation so much worse than someone like Geno, who also had it pretty bad? It was because of False Hope of not being deconfirmed; after seeing all of the Sprits, ATs and Mii Costumes, Shantae fans had thought they had survived. We had been egged on with not only the fact that she survived, but that there was evidence with possible Smash Ultimate references in the Shantae games, and WF being implied to be under a strict NDA. But During the World of Light trailer, Nintendo was basically like "Before we go, we have one final Deconfirmation: Shantae, the Half-Genie Hero will NOT be joining the battle in Super Smash Bros. Ultimate." Basically we survived the Assist Trophy and Mii massacres only to get a sticker; a previously existing PNG file. We got deconfirmed at the last possible second and don't even get to appear on the stage for it. It was similar to Skull Kid, except no one could say "oh hey. They're probably still an AT."