I think it depends on the fleet and the person. The 330/340 has been nothing short of hell for the last 3 years. The flip flop of day and night duties, and the amount of duties during the month, takes it's toll and becomes incredibly debilitating. The F/O's on the 340 have had a decent run of late but the captains are still living with very tough schedules...
I have done short haul, and was tired at times, but I never experienced true fatigue until EK. It's ugly.
I think most are anxiously awaiting the 380
My 2 cents