There is not much you can do. I think the fatigue is caused by a combination of small font sizes, more subtle shadows, brighter colours and flatter overall aesthetics. While I am not getting tired by this, I do share a slight unpleasantness when working with El Capitan. I chose to use Mavericks as my daily driver again and it just feels distinctly better to work with.
In addition to the accessibility settings you already mentioned, make sure you select a bigger sidebar font size in System Preferences > General. You might want to consider installing a plugin to change the fonts to something more legible, like the typeface used in Mavericks (e.g.
here). It also helps to install
f.lux to tone down the brightness and white point. I assume that a higher-resolution display will also help, but you should make sure that you are not sitting too far away from your screen so as to not strain your eyes unnecessarily.