After Endgame, is going to be really, REALLY difficult to find a character who can take Thanos' place as the "top bad guy". But I think I have him: Kang the Conqueror.
Think of it, this is a villain almost impossible to defeat, similar to Thanos. Because it doesn't matter how many times you defeat him, with his time travelling powers, he will always return; over, and over, and over. He has an almost unstoppable army at his commands, he has many faces (Immortus, Scarlet Centurion, Pharaoh Rama-Tut... etc), and he had put several plans through his time traveling manipulations. Finally, the time traveling's plot used by the Avengers to undo Thanos' snap could be the thing that brings Kang to the MCU. I mean, Avenger's manipulations could have been noticed by Kang, who decided to conquer XXI century to avoid another "unacceptable" time travel.
Also, if the Post-Credits scene from "Spider-Man: Far From Home" about S.W.O.R.D. being created serves as a clue, remember that Kang's headquarter is Damocles (as the legendary sword). It almost suits perfectly.