https://www.youtube.com/watch?v=Y_ObH-Ltxdo

Persona 5.
You execute God in a giant kaiju monster battle with an oversized handgun.

Mother Gunship let's you build big guns

Marvel vs Street Fighter; Plasma Ejector
Xcom; Blaster Launcher

引用自 Hammer Of Evil：

Hammer Of Evil 3 hours ago
    
Games with the Biggest Guns?

oh yes. its time.

games with:

infantry held big guns
vehicle mounted big guns

its time we reviewed the biggest guns before we head into the depths of winter in the cold north.

please load your suggestions into the magazine below

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Battlefield 2142; Koenig H-AVR

Twisted Metal had a lot of armaments and being mounted to vehicles would be considered at Biggest.
BF2142 had Titans flying fortresses with minigun anti air and cannons which not sure considered a gun.

Rambo.

Robocops is a hand gun thats got plenty of potential especially now since can be shown on a 65 inch monitor and he's 8 feet tall.

from the depths can easily have an unlimited size of guns as its fully modular and i think also has mod support

same with any other uncapped building game

but if it has to be a non building game then easily doom eternal, helldivers or halo as they all have planet vaporising cannons

doom has a big ♥♥♥♥♥♥♥ gun in it. it shoots big ♥♥♥♥♥♥♥ balls of big green ♥♥♥♥♥♥♥ plasma that fry all the big ♥♥♥♥♥♥♥ hellspawn in town.

Saints Row 4 - Black Hole Launcher

Magicka
has
M60

Tried looking and remembering Wild arms and wasn't really there

Could say FF3(6) has those mechs they have blasters, and later FFs really went with ton o gun.

Alright so there is a Phazer and Blaster in the game Ultima in some part of its many of the series.
There is also a Blaster in Might & Magic Mandate of Heaven which in some small way are the biggest for the game itself being it and Ultima has stopped for some time being made and deserve a mention.