What are the best ways to reduce the memory usage of Safari on Mac OS X?

I have started using an extension called μBlock (that's a Greek letter mu, not a lower-case u). It helps save resources by not downloading or running code associated with ads, and actually makes browsing lighter than having no ad-blocking at all. This is opposed to extensions like Ad Block or the unrelated Ad Block Plus, which add bulk in order to block ads and use more resources than just leaving ads in place. Anyway, it seems to work for me. Safari feels mildly more responsive while μBlock is actively blocking unecessary code from loading. As others have suggested, you might try blocking extras. Click2Plugin will block all plugins like Flash and PDF viewers until you click on them to load them. Script Blocker will disable scripts (except for those common enough and light enough to be on the default whitelist). Of course, loading too many extensions may just end up using the resources you save. Give them a try and see what works best.

Whyever has no one mentioned the superb Safari extension Click-to-Flash by Mark Hoyois, http://hoyois.github.io, which gives you superb control from its preferences page and also from the contextual (right-click, Control-click) menu as desired. His Click-to-Plugin does the same for all your plugins.