I'm not going to say anyone could play a given character, but I'm also not prepared to say that Margot was uniquely qualified to play the character. Granted, I haven't seen Birds of Prey, but from everything I've seen of her she's playing a version of the character that's different from the other versions I know. She made the character her own and did a good job of it, and recasting would be done with the knowledge that that's the version the general audience knows, but it isn't an exact recreation. Jack Nicholson played The Joker in a way that only Jack Nicholson would play him, and people loved it, and then years later Heather Ledger played him in a completely different way. Personally, I liked Nicholson the best and probably always will, but Ledger redefined the character and obviously has a ton of fans.
If they were going to do Harley Quinn in the Reeves' films (I'm not even talking about getting rid of Margot's Harley), I would differentiate her by portraying her in a creepy doll way rather than the action antihero that Robbie's was. Dakota Fanning, Amanda Seyfried, Jena Malone. Don't try to beat Margot at her own game.