Not to be contrarian, but here's my list of three things that will KEEP your Mac awesome:
1. Keep plenty of free space available on the hard drive. Ten percent is a good rule of thumb, though that's just a generalized figure. Mac OS X needs lots of free space to work well.
2. Avoid storing crap on your desktop. It look unprofessional, it makes it easier to accidentally lose things, it's blocking your awesome background, it uses more resources than storing things properly, and its far easier (and a superior solution in every respect) to use aliases and/or the Dock for this.
3. Don't run a zillion menu bar items, cram the Dock completely full, run a bunch of constant background processes, store absolutely everything in one folder and other lazy bad practices. The dock, like the bookmarks bar, like the desktop, is only for the FEW things you GENUINELY need quick access to and works best when you use it like that. Constantly re-evaluate what you're actually using most and least -- get the least-accessed things off your boot drive wherever possible and reserve your one-click access areas ONLY for the stuff you ACTUALLY use all the time.
(and here's a couple more)
4. Do your maintenance every once in a while. I like OnyX but use whatever you want. Every other month or so is fine IMHO.
5. Really learn the Mac before cluttering it up with (mostly) crap. The apps that came with the Mac, along with the OS, have MANY MANY hidden powers and abilities that will amaze you. Find them out -- and once you feel very comfortable with what you have, only THEN will you really know what else you might NEED to get from third-party suppliers.
If you follow all five of these points faithfully, I promise you that (barring mechanical failure) your Mac will a) run well for the entire course of its working life and b) continue to delight you the entire time you own it.