I hate the radscorpians and the mirelurks. They are a pain.
Other than that I haven’t had any trouble really with anyone else. Besides every now and then when I go on a rampage and kill a town and some of the boss guys can be tough since they only go unconcious. Jericho’s pretty tough too. All the characters you can get to join you are really tough to kill besides Dogmeat but even he is stronger than most enemies.