Well, there are actually quite a few people that already can fire .50BMGs (M2HBs) perfectly safely, as in while carrying it (sling and all).
In the end it’s only a matter of personal strength and fortitude, the thing only weighs 80-something pounds (sans ammo, which you’ll need) but actually kicks no worse than the Barret thanks to it (which only kicks as hard as a 12 gauge w/ hunting load… honestly, that thing’s a kitten).
Arnold Schwarzenegger, Sylvester Stallone and a few others have done it off the top of my head… and considering the extent of the Character Creation (and mutations you can end up with), there’s no reason why players couldn’t create people stronger than them…
On the weaker side, Kyle Myers pulled it off for a few moments (or so I’ve heard) and he’s no strongman… although he did hurt himself in the end, thus no video (again, or so I’ve heard), but still.
But I like the large weapons concept, but think that super-humans(?) should be able to use them too somehow.