Is it OK to remove files from any directory named "Caches"?

[I'm not looking for dire warnings from my explanation of why I'm asking this question as I'm aware of the possible consequences and willing to take the chances (and to reload my entire system) but will briefly explain why and add a caution to others who might decide to do the same that if you have any doubt about being able to restore a crippled system on your own then I'd suggest taking a safer route than what is described here. That said…]

Due to intermittent problems of uncertain cause with a system that's been through many upgrades, I'm attempting to clean up some old clutter that has built up over many years before resorting to a completely fresh install that would require reinstalling all applications and restoring all my personal settings. I've got enough professional experience (Mac, Unix & PC), good backups and the ability to recover (which I have) from mistakes that might leave the machine inoperable and am willing to take the risks involved. Various errors in the system logs have pointed towards directories of cache files, most of them quite old (though often recently accessed) that have inconsistencies (valid or not) that might be creating or adding to the current problems. I want to see if removing some or all of the files they contain to see if it might help and know that there are many cache files that can be removed with no problem but don't know if it is generally (or always) the case that it is OK to delete their contents.

I see lots of questions about deleting files from specific cache directories but would like to know if there are any directories that are named "Caches" (literally) whose contents should not be touched? Or will any removed content be recreated as needed? If some are off limits then is there a way of knowing which ones must be left alone?

Also, is there a best way to delete files from "Caches" directories (Single User mode, Recovery Console via Terminal, booting to a system on a different disk from that which you want to change, etc.) that avoids crashing the current system session or having files you attempt to delete be restored during shutdown or restart?