Twenty years ago I did London to Los Angeles in a DC-10-30 (single crew) without an autopilot and I don't remember it being much of a problem. The weather was good at both ends and the situation kept at least one of us from getting bored.
The lack of an autopilot is not an MEL no-go item on my present aircraft and I recently did a 4-sector duty without one.
Both events were unusual in this day and age but it is quite nice to know that I can still fly as well as I did donkey's years ago before such nice things were invented. Mind you, I tend to hand-fly below 20,000 ft anyway unless the weather is crap.
"If in doubt, trim to 90 kts and pick a field".