In addition to the manual options of "Empty Cache" or "Reset Safari" before quitting Safari,
Onyx under Automation has an option to clean "internet cache and history" which its Help describes as follows:
Internet Cache and History: This option deletes stored copies of Internet pages you've visited, temporary files you've downloaded, and the history of pages you've viewed. The browsers recognized are: Safari, Shiira, Internet Explorer, OmniWeb, Camino (formerly Chimera), Netscape, Mozilla, Firefox (formerly Firebird and Phoenix), Opera, iCab, surfDude, SunriseBrowser, Xyle scope and WamCom.
Though I frequently use Onyx clean internet caches function manually, I have not used the automated version.
Tiger Cache Cleaner has many cache cleaning options (a great light, medium and "deep" option which I've found useful for troubleshooting) and internet cache clearing but I didn't see the option to automate it.
This seems like something that would be amenable to a Terminal command or AppleScript or perhaps even Automator (e.g. find the Safari cache folder in Finder and move to Trash - but then you'd still have to manually empty trash.)
