Level up, large caliber sniper, drop them from a distance.
Place a few proximity/bottlecap mines between you and them, shoot them and watch them run at you until they go boom.
Get Oh Baby! and level up your melee with the perk that knocks people down and penetrates blocks.
Level up unarmed and get some of the gloves that cause crippling effects like lost strength or paralysis.
FAT MAN! ALIEN BLASTER! GAUSS RIFLE!
The trick is to level up a particular attack skill and then find a good quality weapon that matches it. They're actually not that tough once you are skilled up and carrying something stronger than a varmint rifle.
If you are heading down to the bottom of the quarry, I personally am a fan of Euclid's C-Finder for one particular Deathclaw (you will recognize it when you see it). Not because you really have to do it that way but because it is really awesome when it works. Orbital strikes FTW! I also like using the C-Finder on single, lonely, already nearly dead bloatflies just trying to escape me. You might not need it for the flies.
