any of the legendary creatures, the overseer ghoul in vault 34 has highest health out of any bad guy,
all of dead money,lots of cazadors so dont go into the hill without good guns and vault 34 can give you a bad time with ghouls and rads. and i guess thats it for me on how can be hard to kill oh and the tunnellers in lonesome road

I think you guys are forgotten one place, Quarry Junction and bagilion of Deathclaws

sigmaceti wrote:

I think you guys are forgotten one place, Quarry Junction and bagilion of Deathclaws

I honestly have to agree with this...Deathclaws aren't fun at all.

Going into the divide when you not ready, if you don't have enough ammo or stimpaks on you, you gonna get your ass handed to you fast!

but I must also agree with sigmaceti and atomicfox, I hate those deathclaw bastards!

old world blues can be very annoying sometimes, expecially when you find yourself caught between a group of lobotomite and one of "Y-17 trauma override harness"

The Courier's Mile in lonesome road was hard to clear ,dethclaws + marked man were annoying to kill because they were healed by the radiation

Since the OP hasn't specified which game, I'll just list them here.
Fallout 1: The Glow, because the radiation hints are very vague and doesn't kill you until later.
Fallout 2: Enclave Oil Rig, fighting Frank Horrigan without any companions.
Fallout 3: Ol' Olney, because of Deathclaws, and they can ambush you if you aren't looking good enough.
Fallout New Vegas: Quarry Junction, Dead Wind Cavern, and Lonesome Road.
The Ending of Dead Money if you are trying to loot all of the Gold Bars + all of the weapons + all of the armors, and escape unseen from Elijah.

Hardest area is Dead money/Sierra Madre map because Elijah took all your equipment, and even if he didn't , you can't kill holographic guards, can you, and even if you can there are those speakers and radios
Only one enemy is worse than Deathclaw and that's Cazador or better say Cazadors ( you won't see any alone ), I just hate those bastards, and their poison ... hope they'll cut them from the next game

Ever been cornered by super mutants in a room with nothing but a few pulse mines and a single stimpack? Playing Fallout 3, I ran into this situation. I believe it was in the National Archives, in the area immediately before the one where the "secret" elevator came down. I don't think I've ever "Loaded my last save" any more times than I did in that one room.

I had to turn the difficulty down to have any hope of getting out. I wish I hadn't had to have done that, but if I hadn't, I might still be stuck there. This happened back in July.

lol me (like many others) proably went through sloan and into Quarry junction like "Whats that big black thing with claws over there in the distance??" and then next thing you know youre loading a saved game back the Sloan thinking "WHAT THE #ELL WAS THAT" lol but yea for me would be the Deathclaw Mother.

Worst and strongest enemy of all time in the wasteland ?? Hmm...I d say...Bob the sponge !!!! No just kidding guyz, sorry i'll go take my medication