In terms of mixing or mastering (DIY of course !):
I'd like to throw both the room and the monitors into the equation. In other words you may have good reference monitors yet the sound acquires 'color' or emphasis in certain freqs while traveling thru the air in the room to your ears. These additional freqs may be in what your ears hear as a harsh region, maybe 3KHz thru 4KHz, and your ear gets fatigued quicker when there is a bump in that region.
But generally I tend to listen in 20-30 minute blocks using near-fields and mid-fields when trying to really fine tune something - then take a break for 20 minutes. Your ear and brain tend to get-used to certain elements over the period of minutes. After 15 minutes or so that 1/2 octave bump you put at 12KHz tends to sound more neutral than it first did so I should bump it up some more right ? Ha Ha tricky. eh ?
Another aspect is exactly what you can imagine. If you're trying to fine tune a guitar sound that centers around 1.5K-2.5KHz or so it doesn't take your ears long to get tired and fatigued listening in that range.
So for me I try to get an affordable flat sounding reference speaker, flat reference amp, set up the room so I don't get reflection and freq imbalance issues, and take breaks.
Also by keeping some great reference material handy you can somewhat keep your ears fresh during a long rebalance session by listening to some really well balanced (eq & dynamics) material.
If someone has mixed or pre-mastered something on non-reference speakers with 'scooped-out' mids then you will be listening to a bunch of mids for a while on your flatter response reference speakers. My ears get fatigued just thinking about that !
There's more to it than that, if you look at a Fletcher-Munson curve you can see where your ears sensitivity points are at various SPL. If I listen to hi-midrange for a long time that's what kills me, especially at mixing levels of 85-90dB SPL. You don't usually want to solo a freq range out of a mix but sometimes it happens as well as the fact that the mids may just be out of balance (bad mix as they say !).
kylen