I can't speak for difficulty level of Fallout 1 or 2 but 3 and NV where pretty fun. It's fun being an unmatched one man army but sometimes i wish there of a challenge without the need of self imposed challenges...
I think resources should be a little more scarce, you really shouldn't be able to have around 300 stimpaks or like 200 Rad-Aways. Ammo should be scarce as well. Players should really be encouraged to invest in building up a melee or unarmed skill set.
Radiation Sickness should play a bigger part in the game. I wouldn't say the perks that center around radiation would be mandatory but as it stands they are pretty much an after thought.
They could also limit the amount of weapons you can have on your person. You can still loot and collect weapons and have them in your pack but you have to specifically hot key the weapons you will use in battle and you are limited too like your main gun which would be like a Rifle, Shotgun, Big Gun pretty much any two-handed weapon. Than you have a side-arm which would be like a handgun, and finally you have a melee weapon or unarmed weapon. While in battle you can't open your pip-boy and switch to a weapon that is more favorable for the situation your stuck with what you equip on your person
How would you make the game challenging without destroying the fun factor?