Hd800 ear fatigue

Try breaking the HD800 (and the rest of your rig) in for at least 100-150 hours. Do that by normal music playback at somwhere between medium to high volume - not too loud though!! Then your HD800 will be much more pleasing to your ears. 

Our ears are priceless. Rest your ears. Let your amp and headphones play even out of your ear. They need burn it. Leave it before you sleep. Turn off in the morning. Again, leave it before you sleep, etc. Count the number of hours. If it reached 100, you can put back to your ears. Then do again, for the 200 hours! and so on!

When the speaker unit is brand new from the factory the moving parts are very stiff and not as flexible in the moving coil and the soft fiber / rubber parts as they should be. Therefore a brand new speaker never plays the way it should because it can not move 100% freely. Give it some motion and the parts are softened to become as they are supposed to. This takes a few hours and most people will not notice it. That is what they call break-in or burn-in. Most speaker producing companies does that for you before the speaker leaves the factory.

Listening fatigue is often one of the subtle ways of noticing that the speaker/headphone does sound a bit more sharp and edgy than it is supposed to. Over time it mellows out and becomes more pleasing to your ears. 

I had the exact same problem you described, I usually use my headphone for extended period of time since I not only use them for music but also gaming and watching movies. I bought a pair of Sennheiser HD-800 from here without listening to them before, I did so because it's literally impossible to get access to high-end headphones where I live and by the review they seem to be the best choice.

My previous headphone were the DT-880 and as soon as I tried the Sennheiser I knew they would not be for me, if you're coming from the 650 which are on the dark side (no pun intended), I'm not surprise you found the 800 to be tiring, because honestly to me they are. You might be told that changing the stock cable or the amp will help and while this might be true to some extent changing to another headphone is still the best solution.

You should consider the LCD-2, it's usualy agreed here that if you like the 650, you will love the LCD-2, which can't told for the 650 vs 800 since they are completly different headphones beside being from the same brand.