I personally preferred lumping all guns into a "Marksmanship" or simply "guns" skill, including energy weapons. I believe JES wanted to go that route with VB. Big guns would have strength and possibly endurance requirements. Energy weapons would be limited by rarity, cost of ammo, and perhaps difficulty in maintenance.
I would also favor upping the power of big guns and giving them their own skill, as that is fairly logical, but using them should be a commitment due to the weight of the gun and the ammo. A minigun would not be something you would casually carry around. You'd scout out an area, then return to your hideout to get it. Same with the bazooka or flamer.
Yes I get that RPG players love to be limited in one category while being good in another, but if you are a crack shot with an old school rifle, I don't see why you wouldn't be a crack shot with a laser gun. With the FO3 repair model, it might be possible to make it so you can't get them past a certain condition without using your science (or computer, as I would prefer) skill, which would be interesting.