It's a diminishing returns trade-off. Beyond a certain point you're putting in too much effort for too little reward. This point is entirely personal and based on:
1. your enjoyment of the process itself.
2. the actual real-world performance increase.
3. your perceived value of the performance increase factored over the lifetime of the system.
4. the time and effort put in balanced with your current salary and time availability.
When I was a student, every Hz counted, I had the time, no salary, enjoyed the process and valued the increase more since it meant getting closer to a decent FPS in the twitch games I used to play on my "out-of-date but all I can afford" hardware.
Nowadays I don't bother to put nearly as much effort in, but get around 90% of the way to the increase I would achieve with student-level effort.
Oh and... WATERCOOLING! ... with a large radiator, large diameter tubing, quiet high-flow pump and big slow fans.
