Macs aren't like Windows where gunk accumulates in a central location like the Registry (which prompts the need to run programs like "Cr*p Cleaner" and other Registry cleaning tools). Even the "Repair Permissions" voodoo has become unnecessary since Tiger. The hard drive defragments itself. So there really isn't a pressing need for a spring cleaning.

One thing you can do is delete programs you're not using, or move them to an unmounted disk image. If having a few old configuration files bothers you, use AppZapper to remove all traces of old programs.

Another thing, check your startup items (Users preference pane) and remove any items that may have been inserted by various programs you've installed that you're not using any more.