Obviously designing an airliner to be flown single pilot would be pretty easy - that tech already exists and the loss of safety that entailed from a human factors point of view could be mitigated to a certain extent by more innovative flight deck and avionics design.
However presumably in order for the travelling public to accept single pilot operations there would have to be a system whereby a computer or human monitored a number of flights and was ready to take over in the event of one of the pilots being incapacitated. An actual viable monitoring system like that could be used in real airline service is probably still a long way off.
The system would also have to be able to react very quickly in the event of something happening to the pilot at a critical moment like take off or landing - perhaps that problem could be surmounted by making all take offs and landings automatic.
Just having a single pilot airliner with no back up at all is not something the travelling public would accept...I would have thought.