I, too, have been building my own since the 70s (my first was an Altair 8800 running Microsoft Basic!!) and have actually never bought a 'turnkey' desktop system. In the early 80s some of us at Hewlett-Packard got a version of a MIDI sequencer and Sysex backup going on a few of these. I have had experience with laptops and music and there are a couple of things that are not tweaks, but rather completely mainstream that are important:
1. Don't ever expect good performance with the system load from the vendor with all the advertising, teaser applications, etc. Do a fresh system load from an OEM loader disc...you can use the same Microsoft registration code, if you load up the same system...I have always used the Professional version systems, as there are always a few important capabilities available...mostly around networking/shares
2. Load only what you must....don't put Microsoft Office or Adobe products on the system, as they are ugly culprits.
3. Disable all auto-updates, but make yourself a schedule of updating.
4. Learn about page files, and set up yours as static (i.e. not resizeable) using 30-40% of your RAM.
5. If you are going to use a browser, use Chrome...it is the most secure, and least evil.
6. For me, audible noise is important, so I have, for the last decade or more, used high-tech internal cooling (i.e. heatpipes or monster heat spreaders with low-speed, variable speed fans of large diameter...these are the quietest and coolest. My Shuttle system puts a lot of stuff in a very small box, but it is silent with some of the lowest disk/CPU temperatures that I have managed to see.
7. Get familiar with Mike Lin's startup management tools and use them slavishly to get clean system starts.
http://www.mlin.net/StartupMonitor.shtml8. Don't use encryption (you would be surprised how many people don't pay attention to this)
9. Don't make your expectation of building your own to be mainly about saving money...make it about getting the absolute best system you can while gaining the knowledge of why it is the way it is...
The list could go on....but these are some of the obvious ones