i have a character that use rifle for normal encounter and big gun for tough fight. sometime when i feel like fun i will bring my Boardsider, Minigun, Galting Gun, Missle Launcher (have to use power armor to bring them all)
btw all of below are base on level 50 in survival mode, and 5/5 perks in big gun
Boardsider - Very good against big creatures like deathclaw, radscopion. good shortrange, with upgrade you can shoot 3 canon balls. my general weapons for shortrange deathclaw encounter
Minigun - Very good against swarm of weak enemy. There is a building that got like 20+ feral ghoul and will just swarm you, i just bring my minigun and spray them. they are either dead or all of their limbs are detached for you to execute them. not good against tough enemy even super mutant. they just eat too much bullets
Gatling Gun - Good strong general usage weapon with the damage upgrade, you shoot slower but stronger attack also got good range and accuracy. It is like automatic laser rifle but stronger. my weapon of choice if going against lot of super mutant, gunner...etc
Missle Launcher - Upgrade with quad barrel with targeting system. shoot and forget. got a deathclaw matriarch lurking far away? mark and shoot. got a mirkluke queen spitting acid to your face? mark and shoot. got a scary behemoth coming to you? mark and shoot. none of them can eat more than 2 missles and with your reliable auto target system you can gurantee hit
Fat Man - just for fun. totally not practicle. but while you at it, mod it for MIRV for shooting cluster of mini nukes. because why not?