If you're using guns I'd probably say the Anti-Material Rifle or Sniper Rifle with AP ammo. Are you talking about Guns, Energy Weapons, or Melee?
Yeah I was talking about guns. energy weapons seems useless on them. I do use fully loaded mod sniper and anti material rifle at afar. Whats best at up close?
The AM rifle shoots way too slow unless you're sniping and then a good old sniper rifle will do. A Brush Gun or Trail Carbine with SWC hand loads will make short work of them too. Just wear some decent armor so you have time to work.
When I went through that part on my gunner I used my ranger sequoia but it was slow going, thankfully the first super mutant I killed dropped a decent-condition minigun and the rest of the mountain was cake.