I run Onyx about twice or thrice a year, and the biggest thing that seems to speed the system up (just a wee bit... it never really slows down, actually) is reindexing Spotlight.
Also, I repair my permissions in the Disk Utility once in the odd blue moon, and that seems to make a difference some also.
You don't need to run the app - it certainly won't hurt it if you do (less you go overboard ... I think), but it's not mandatory.