One bullet is all I need... or six fusion cells on a jury-rigged laser rifle of death.
So, this is partially inspired by a video I watched which someone claimed their sniper rifle was the best in the game. To explain it, the guy calculated his Suppressed Instigating .50 Sniper Rifle (named Reason) to deal up to 2596 damage per shot (With Calmex: 5192). Quite impressive, right? Well, I'm certain we can do better.
An Instigating Six-crank Laser Musket can deal over 4900 damage per shot under the same circumstances. A Laser Musket, without any modifiers or perks, with a long barrel, deals 36 damage per cell. With the maximum crank capacitor, it deals 36*6 damage, or 216 damage. Rifleman doubles this to 432 damage per shot. Bloody Mess and Lady Killer/Black Widow adds an additional 15% damage each (Bloody Mess in general, BW/LK against opposite gender), buffing the total up to 561.6. Add in the sneak attack bonus of 3.5x from Ninja, and you get an incredible 1965.6 damage. With the Instigating prefix, that damage is doubled against full health targets, turning it into 3931.2 damage. Psycho adds another 25% damage, taking that and making it deal 4914 damage (with Calmex: 9828).
Now, that is the most ideal circumstance. It's assuming the target you're up against is the opposite gender of your own, they're at full health, and that you use Psycho. For non-humanoid targets such as Deathclaws without the help of drugs, that is still 3,477.6 damage per shot, 40% more than what Reason does.
Probably now you're wondering just how useful this is. Well, it's perfect for the discerning Tunnel Snake who's scared of Radroaches as it *might* kill them! Seriously though, it isn't very surprising that this is just more overkill to most enemies, and it's only really noticeable on a very small number of enemies, the ones which can take more than a single hit from the Sniper Rifle. As such, a normal Sniper is still a better weapon for sniping than a suped-up Laser Musket because it's got a higher RoF and can be suppressed, but if you want to deal the absolute maximum amount of damage, this is how. Enjoy!