I would be for it if It Was more neutering the weapons ability with low stats as apposed to being unusable.
Take the 50 cal for instance, have a check for say, if <40 Strength, -50 accuracy, and +10 tus to simulate both a runaway gun, and stumbling from the blast.
Actually I'd like this because sometimes some guns can feel cheapish if they aren't massive weight or something. I could see it apply in other ways, like accuracy under x decreasing max range before falloff for certain guns like shotguns. Especially if you made it similar to overweight, in every point over could make the effect more severe.
The key here is making it optional to be GRADUAL, and not just impossible to use. Rpgs that do this seem better imo, if guns or swords can be used by anyone, but in unskilled hands have bad aim, slower operation, and other problems. Like deus ex, you can use any gun with any build, but using the flamethrower is not viable unless you are specd for it because you move slow unless you are trained in heavy weapons. Doesn't stop you from slowly waddling towards terrorists with a gun too big for you, but you have the OPTION, except for certain circumstances.
I also agree about a per class, or per armor restriction for certain equipment, which is funny because I made a thread about that I think.