In real life zweihanders and other such oversized weaponry had specialized uses. I believe blades as big as Sephiroth's would be held by multiple people with the explicit purpose of clearing out infantry sorties. Zweihanders like Cloud's were mainly used to knock pikes out of people's hands on the front lines. I had the theory you would wield one as far as you could and destroy a bunch of distracted people, then drop it for a more functionally appropriate weapon when the situation got hairy and someone had you in their crosshairs.
I believe I was close, sans the pikes thing, which my friend told me about.
However, the inhuman strength necessary to wield one practically in a combat situation is reserved for a special few, and their zweihanders aren't as thick or immense as Cloud's greatsword. There have been some men historically who would decapitate multiple people with a single swing and fought with zweihanders like Guts does, but I don't think that would work with the Buster Sword. Too thick.
Built for mako and cell infused super soldiers I'm afraid.