Two spring to mind. First was a long time ago; C130 12 hr night flight Port Stanley to Ascension,heavy thunderstorms,icing, mod turb for most of the trip, wx on mins for landing and total autopilot failure at 1000' on climbout!
Second was similar wx, but a 20 min positioning flight MAN LUT with a very skittish 64 tonne 757. I was equally knackered after both flights