What's the best way to do it? Assuming you have full ranks in Better Criticals and all of the relevant weapon/magazine perks.

I'm putting my money on an Instigating Calibrated Sawed-Off Shotgun at point-blank range, myself. There's very few things a critical hit from that thing couldn't kill, and this was without Better Criticals on my character.

Another question for Lucky characters: How often are you pulling off crits?

I added 25% crit chance though the console, so my random hits can crit (I don't use VATS).

Ninja VATS is an overpowered build. 5.3x bonus ranged damage, 10x sneak bonus melee damage, and 15% bonus damage on men. But NINJA VATS is the best way to do sniper 1 shot kills. Here's my build. Level 68. PS4. No mods because cheating on FO4 is pathetic. It's an easy game. Even on Survival.

STR 1

PER 3 - Rifleman 5/5, Awareness 1/1

END 7 - Perks are for survival here. No damage bonuses.

CHR 3 - Black Widow 3/3

INT 6 - Gun Nut 4/4

AGI 10 - Gunslinger 5/5, Sneak 5/5, Mister Sandman 3/3, NINJA 3/3

LUCK 7 -Better Criticals 3/3, Critical Banker 3/3

I've been using VATS less often now because I run around in my Power Armor and VATS drains fusion cores fast. But I still get to 1 shot most enemies with my Relentless 50 cal sniper rifle. I use VATS on deathclaws, behemoths and senty bots.

There are also legendary weapons that do like 50% more damage if the target is at full health or something.

With Cloak and Dagger, Sandman 3 and Ninja 3 you should be able to get up to 6.3x sneak attack critical hits with a silenced weapon.

Ya. I forgot to mention that. I have an Instigating Semi Automatic Rifle 308. That thing is beastmode.

Depends on the enemy.

Some will be dead with a single swipe of a machete.

Other foes have base health of over 1000 with high damage resistance.

For instance a Super Mutant Warlord has health of 1500 plus so it would be hard to kill in one blow compared to a regular supermutant of 120 health.

Max out your Sneak, Ninja, and Mister Sandman perks, and get Deacon's perk and you can get something like a 6.1x sneak attack multiplier with ranged, suppressed weapons. That's usually all it takes.

I have an instigating .50 sniper rifle, which does double damage at full health. So combined with all of these perks I can get like a 12.2x damage multiplier for a sneak attack when the enemy is at full health.

VATS can go die in a fire, I like my crits in real time.

Well I play on "Normal" so maybe that doesn't apply to your situation but . . . Ever since about level 30? (the toon is now level 78) I've been able to pretty consistently get one shot one kill headshots on most Super Mutants (not the boss tier variants but the more common ones). Even just fully modded, non-legendary .50 cal without any Ninja perks and 3 or 4 Rifleman perks along with Sneak (but I don't think that applies to damage at all) was enough for me.

Now that she has a Freezing Gauss rifle (485 base damage and +25 freezing) at level 78, I can literally one-shot most things in the game *sigh* Mirelurk Queen took about 4 shots with that gauss rifle.

The main problem I have with sniping is that some critters are 'twitchy' and it seems like some of them 'react' to having your cursor put on them by moving around more erratically (even when you are completely undetected and so far away they wouldn't even detect you if you stood up). It seems a bit random. Sometimes a raider or ghoul even a Super Mutant will just stand there still as a statue, other times they are fidgety as a heck.

On the whole, I think they did a good job with whatever is going on behind the scenes to make sniping more interesting compared to FO3 and FONV.

DAMN! That much!? I've killed a few of those guys, but I don't think I've ever one-shotted one

Alas, the only thing I've found "Instigating" on is a Gatling Laser (with it's amazing sub-20 damage per shot).

My sniper rifle is +50% damage to robots, but I don't have any of the crit perks, so I don't really one-shot any bots except for weaker Protectrons.

I'm talking about VATS criticals specifically, not sneak attacks.

Vats Crit pistol build with a two shot plasma pistol with the crit dmg mod, 1 shots almost anything and no sneak required. It might sometimes take 2-4 shots for big high level legendaries, but it doesn't matter you get like 12 vats shots and spam crits all day. No time wasted sneaking.