I don't have an issue using mine one handed, my hands are fairly average, maybe a bit larger than average. What I normally do is reposition the phone on my palm slightly whenever I need to reach. It's not something I would do while walking or if I have the chance to be jostled or moved.
But the past few years I've trained myself to use my phone differently, I grip it hard when it goes in/out of my pocket and am very careful with it overall so I feel comfortable carrying it around without a case or screen protector. It's this trained awareness of my phone which I think has saved me from any accidents.
It's definitely a trade off, but a worthy one IMO. Once you use that humungous screen you will never ever want to go back.