I don't have big hands, but I am typing this one handed on the S4 & really only use 2 hands for playing games. I cradle the phone on my pinky between the 1st and 2nd knuckles and can reach all corners with my thumb even with a case on the phone. If Apple showed people holding the iPhone so they could use all the articulation of their thumb and palm rather than the stupid, stunted tyrannosaur way they do now, we'd probably have a 4.7 inch iPhone. If there was widespread developer usage of gestures and auto hiding, a 4.3 inch iPhone could be great (after a jailbreak to enable the basic functionality I need in a phone).
Regardless, I draw the line at 5 inches. Any bigger and the entire thing becomes oddly balanced and fits poorly for my needs.