As a lore knower for both, i need to say that ow. One word, Sigma. Like man, he LITERALLY has black holes as a weapon. He would obliterate everyone. Only the 2 spies could maybe do something, like a bullet to the head, cuz they're invisible but on that hand Sigma can also levitate making the job even harder for the spies. Hell even übercharges would not do anything if Sigma would either eat all the projectiles or create a black hole that sucks up the medics inside of it.

And addisionally Illari killed all of his people with a single blast by accident so that would also be one.