There are several ways of looking at this:
First, "single pilot operations" by the way of flights with a long cruise portion. I can see that happening in 5-10 years, with one guy at the controls and the other taking rest somewhere quiet and comfortable, then swapping over. In some ways on flights of a certain length, it could be argued that it's safer than the present arrangement where both pilots get the opportunity to get tired because most seats and flight decks are not the best places to recuperate in. The autopilot would probably have to be certified not to disconnect, so the remaining aviator could answer a call of nature without undue worry. There would likely be classes of airspace, datalink capabilities, medical and other requirements included in the rules - like a kind of EROPS+.
Second, only one pilot on board. Yes, there are lots of single-pilot commercial operations that go on around the world but most authorities limit them to relatively small aircraft. The accident statistics in that area are not encouraging, possibly partly to do with performance and certification rather than one pilot per se, but it would be a brave regulator who went first to up the limits.
I think there will inevitably be pilotless aircraft at some point in the future. I don't think we need to worry too much as by then anything that was previously done by a human will be much better performed by AI. We'll all be living in total hedonism, dead or stuck in some virtuality (or all three!)