Certainly.
I already spoke to the frequency of takeoffs and landings. They're definitely the most taxing portions of the flight. The length of the flight is a consideration: the longer you go, obviously, your time on task is going to be longer.
The other consideration is the circadian rhythm. On top of that, the reason we're focusing on the time between 5 p.m. and midnight is that if you take off with an unaugmented crew at that time, you're going to be landing overseas in your window of circadian low, without proper augmentation on board. Flights less than eight and a half hours, sure, but when you're looking at flights over eight and a half hours, the science is very clear: NASA science says eight and a half hours.