Personally, I consider Lekain to be the main villain of the game. He's directly responsible for the atrocities in Daein which leads to the events in part one. He has no relevance in part two except for the Begnion dracoknights going into Crimea which wouldn't have happened if it weren't for the corruption of Begnion's Senate. In part three, he's the reason everything bad happens such as the Laguz being provoked, the blood pacts, the coup, Valtome being appointed as leader and provoking Crimea. In part 4, he no longer has as much relevance but he still has more screen time until his death.
All Sephiran does in part 3 is get captured and later on conducts an uprising. In part one, he sends the Black Knight to protect Micaiah.
He does end up convincing Ashera to pass her judgement but Ashera really didn't need convincing.
I don't think Ashera constitutes as the main villain because she only becomes relevant in part 4 and wasn't even the cause of all the calamities.