This might be a controversial take but geniuenly Aerith and Tifa are the two biggest threats to Sephiroth and its not even close.
Aerith is Sephiroth's foil, the opponent who the planet has deemed as its champion, because who better to outsmart you than someone who shares so many of your experiences and yet is your opposite in every way.
I don't think Aerith was given all this knowledge of the future because she's the last Cetra, but because she's Aerith. She is the strongest threat to Sephiroth's power not because of her blood but because of her brain and her heart. She holds a love inside her not just for the planet, but for everyone and everything that lives on it, too. She has a wit like no one else's, nothing slips past her notice, and she is willing to give up the one thing she wants most—a future for herself—to ensure the future of everyone else.
Tifa, on the other hand, while lacking Aerith's knowledge if the future and connection to the Planet, has a passion inside her that surpasses the ambition of Sephiroth. She is his victim more than anyone else, the one to get caught in the crossfire of the cycle of abuse started by Shinra, and she will be the one to put an end to that same cycle in every single universe.
Tifa again and again acts in ways that Sephiroth doesn't know how to counter because all of her anger and passion and drive is fueled by love and he could never understand that.
Sephiroth sees Cloud as a pawn he can control, but Aerith and Tifa are the ones blocking his path time and time again.
Sephiroth is alone in his fight, but Tifa and Aerith are not. They hear what the other doesn't speak out loud. They help eachother live in the moment. They always pull eachother back up. Their roles in combat even compliment eachother.
There is no one more essential to the fight against Sephiroth than those two, not even Cloud.