I covered a lot of this in another thread concerning big guns and DU-rounds.
Against a given target the Law of Diminishing Returns applies to the size of the weapon you hit it with. I challenge anyone to really tell me what difference it makes if you hit a human target in the chest with a .50 cal round vs a 120mm round. Both create a cratered chest and the target is dead. The extra energy of the 120mm round (this is what most modern tanks mount and fire as their main gun) over the .50 cal round is wasted. It is, literally, blow through.
The same applies to the difference between a .50 cal round and the more common military grade rifle rounds (7.62mm, 5.56mm, .308 cal). The advantage gained by using a .50 rifle is in range and armor penetration. Not in soft tissue damage. You can always find a group of gun-bunnies that can talk for hours and hours about the intricacies of tissue damage profiles of the various rounds and give you just as many anecdotal, one-off, war-stories they've heard about. Most of it is just talk trying to make a mountain out of a mole hill aimed at trying to justify "Cool Factor". Yes, the .50 will cause more tissue damage. But that extra damage is, in every way, purely academic.
The way I would model these big rifles and other esoteric and/or military grade weapons is through 3 means:
1) AP. I can't remember if this is actually in the book or if I just invented this right now.
But if you are using something designed and purposed to penetrate armor (like a .50 cal with a tungsten penetrating core), I give it a AP rating. This basically means that this round ignores that many levels of Armor. No extra damage.
2) Aspects. Simple, flexible, quick and non-game breaking. The player declares that he is loading "Ammo X" and gains a free tag on the Aspect "Super Ammo X" for +2 or an Invoke of some sort.
3) Massive damage catch. Think Ghouls and Uber-ghouls.
Oh, and yea. Hit these guys with the Resources and Crafting checks for this stuff.