I play on normal difficulty, as I am not actually looking for too much of a challenge (I avoid stress). I no doubt could easily play at a harder level because I rarely take even 10% damage, and that's only when I don't pay attention. However on normal I normally one shot enemies, super mutant masters included. I have invested in the appropriate damage perks for my weapons (rifleman) as well as maxing gun nut. Also I am quite good at placing head shots even when the enemy is aware of me and charging. I should note that I do not use VATS, ever, and that very likely changes my experience. For one, playing without VATS does in theory make your game harder, so my normal is probably as hard as someone else's harder. I also use weapons that maximize damage. My go to weapon is generally the
Spoiler Overseer's Guardian with a 'Two Shot' legendary
. For really big stuff I carry an instigating Gauss Rifle which can one shot death claws with a head shot. (I had a two shot gauss rifle in my previous game, which I am studiously hoping for for this lasted character.)
One shotting enemies that are aware of me is not always possible even with my legendary weapon mods and head shots, so I generally play as a sniper and take out most enemies from stealth. Sometimes I have to step into a room with multiple enemies which can get tricky with stealth. I have found though that if you head shot them fast enough, you can still get the stealth bonus, as it seems to take them more than a second to really figure out where you are. If you are engaged with multiple opponents and you are no longer able to one shot them due to having lost the stealth bonus, duck back under cover and move away until you can reacquire stealth.
If you are still having problems with one shot kills, consider picking up the Ninja perk. Maxing out rifleman, ninja and bloody mess (and gun nut), and using a two shot or instigating gauss rifle can make one shotting behemoths possible from stealth.