Chris;
For Mr. Optimistic, I can offer my own experience at hand-flying the A320, A333, A343 & A345 up to, at, and down from cruise altitude is that they are easy and "normal" to fly. In Normal Law the aircraft is not unstable. I suspect that it is the same in Alternate and Direct Laws but with degraded "damping", one must be very gentle with the aircraft. It's hard work as one is making small corrections all the time, but it is not difficult to fly in the sense that it is unstable. I've only flown Alternate and Direct Laws at cruise altitude in the sim.
The fact that autopilots and now FBW are installed doesn't mean the aircraft are manually unflyable at cruise altitude, but as we move further away from actually flying the machine, we also lose touch with our environment, which is extremely thin air with consequently much lower damping properties.
So one has to be smooth and gentle with the controls and never make large control inputs or stick movements. It doesn't require unusually good hands but it does require practised hands.
As Chris Scott has observed elsewhere, PIO can be a reality in any aircraft being flown at cruise altitudes but without its own damping abilities. One simply never took the yaw damper off the DC9 or DC8 for example.
I hope this helps.