To be honest...
... I am glad of a separate thread...
We all know crashes are multifactorial. Fatigue is one factor often enough. A real and significant factor. But it is boring to hear it 100 times on every thread. Because we all know already.
There are three answers to fatigue. (1) get more sleep. Okay, not likely in today's world. (2) learn to do it in your sleep. I reckon you could pretty much throw anything at Sully. (3) rely on automation to take the strain.
I like answer 2, I do. But Sully's are hard to come by. And fatigue is not just the domain of the ME, it wasn't long ago that it was the scourge of the US regional lines. Calgon 3407... Stall warning... PF pulled up. If there is one thing you should learn to do in your sleep it is how to handle a stall warning at altitude.
Today's reality is (1) or (3). You are lucky if you can get (1). Most will be in (3) territory. And that is how it will go.
Every day I take a driverless train. It runs smoothly and predictably. How long will it be before pilotless aircraft? And how will its performance compare? It isn't far away.
No doubt some will crash. As do the ones with pilots. But would it be worse? I can't see them heading off to the southern Indian ocean..
Just to play devils advocate....