There are already many single-pilot commercial operations being done in single-pilot certified business jets and turboprops. Yes, it's slightly harder work, especially in terminal airspace and on the ground, but it's by no means impossible or remarkable. At its best, I've found it very rewarding and enjoyable.
The fact that in the end, money drives everything in today's aviation, suggests to me that single-pilot airline operations are likely to come eventually, provided that someone doesn't come up with a comprehensive argument built around the high frequency of gastro-related incapacitation.
I would definitely prefer to fly alone than with the least competent colleagues I've encountered, though they make a very small percentage of all those I've worked with.