Unlike Windows machines, you don't really have to do anything to keep things clean. The thing I would recommend is whenever you want to uninstall programs (any that don't have a built-in installer), use a program like AppCleaner to remove application so that all associated configuration files go to the trash as well.
This doesn't necessarily slow things down and doesn't take up a lot of space, but just completes the uninstallation.
Other than that, you can run OnyX at some interval to clean things up and a Repair Permissions from Disk Utility might not be a bad idea.
I've been using my iMac since I got it in early 2009..upgraded it to Lion and Mountain Lion and do nothing special with it other than use it..no anti-virus, no checks or anything..