Good posts so far!
Listening fatigue is the one thing we must avoid at all costs, as Scotty said it will lead to not wanting to listen to music and turning the volume down lower so it's not so irritating. Producing products that do not contribute to listening fatigue is my #1 priority, I will not make compromises in this area as I believe owning components and cables that do not cause fatigue is key to our long term enjoyment of music.
Many things can cause listening fatigue, high levels of distortion are very obvious and cause it quickly, but there are other distortions that may not be measurable that contribute, I find it's mostly the material that the electrons flow through that causes these lower level distortions and a kind of listening fatigue that is hard to identify and can remain unconscious, poisoning enjoyment of music. Cheap connectors are the most prevalent, it's best to replace connectors with ones made of pure copper. Lower purity (4N and lower) silver wire accentuated leading edges and causes harshness, it's best to avoid any silver with the exception of UPOCC silver, which may be the most accurate conductor material available.
Noise on the AC power supply causes listening fatigue too, this can be very obvious with dirty AC power but can be low-level like cheap connectors and cables if it's lower levels of noise on the AC line.
Poor vibration control may also cause fatigue, a good example is speakers spiked directly to a concrete floor... the better your vibration control the less fatigue you will have.
Cheap passive parts can also be an issue... unbypassed electrolytic caps directly in the signal path or last stage of a power supply, cheap resistors, etc...
If you want a system that has the least amount of fatigue possible you must start with components that are designed properly, then address AC power using a good emi/rfi filter, deliver the AC power with top quality power cables that use pure copper connectors, plug them into IEC jacks that are also made of pure copper. Start at your source and replace all RCA or XLR jacks with pure copper units, same with binding posts.
There are also parts that cause issues that are the opposite of listening fatigue, these are parts of the system that add warmth while smearing detail. While not as bad as fatigue, the loss of detail will prevent a satisfying connection with the music. Cheap copper wire used in IC cables does the most harm, bad IC cables will completely get rid of spatial cues, reverb trails and other fine detail that should be present in the music. Improperly used passive parts, such as some carbon resistors like Kiwame will also add warmth and obliterate detail. My design goals are to preserve as much fine detail as possible while not adding distortions that can cause fatigue. In my less expensive cables I do make compromises that add warmth and reduce resolution in order to meet price points. It is much better to have a smooth, warm component than a grainy, harsh component, but neither are ultimately a good component.
Listening fatigue happens a lot faster at higher volumes, I tend to test at high volumes so it's more obvious. You should be able to listen to your system at realistic volumes without fatigue.
I am also convinced there is a correlation between certain kinds of distortion and hearing damage. A clean system is much less likely to damage your hearing vs a harsh system played at the same SPLs.
