To me, fatigue can come in the form of ear-piercing highs, sibilants in the mids, and boomy bass. I can't last very long listening to these characteristics in an audio system. Sometimes one or 2 can be present in a system, but if all are present, then probably I won't last five minutes.
There is a "good" fatigue that can come in; if the system is truly working well the intensity of the sound is very satisfying but there comes a point where perhaps a more appropriate word than tired to use is replete. You are satiated on the emotional experience, so your mind and body says, now do something completely different to balance the senses. Solid rock & roll at high levels for a whole album, say, will do it for me: time to go out and chop some wood ...
This is totally different from feeling crappy and out of sorts because the sound just isn't right.
To throw in my two cents - I would say that some of us probably suffer from listening fatigue more that others and that's a genetic thing. A certain sensitivity in hearing can run in a family. I know it does in mine. One of our younger sisters, for example, cannot listen to MP3s. They give her a headache.
If I use headphones, the slightest bit of distortion will drive me nuts and I'll be lucky to even be able to listen through a single song, whereas some may not even be able to detect that there's anything wrong. Generally, it seems, distortion in the highs and bass does me in faster. For me personally, I cannot stand headphones for too long. Even the really good, expensive audiophile headphones. Having the sound centered in my head creates listening fatigue very quickly.
During my copious free time away from Genesis (haha!) I review the occasional headset for a gaming web site. If I can make it through a 4 hour gaming session and am not ready to toss my cookies, they aren't bad headsets.
Carol-I too detest headphones. I find them to be very unnatural. When I was at the RMAF, I tried to listen to some mc transformers that a vendor had setup to listen to via a Sony TT and a pair of cans. After a few seconds, I took the cans off and told the guy I just couldn’t listen through them.