While installing Mac software is often as easy as a click, uninstalling takes a bit more work. Rather than hunt around for preference files, etc. I use AppZapper. By simply dropping an app onto the cute raygun icon, AppZapper finds all of that application's related files -- preferences, caches, etc. -- and lists them in a window. With a click, it "zaps" them (you can disable that sound effect) to the trash.
Fortunately, they aren't deleted for good, so you can recover something zapped by mistake. Once you're ready, simply empty the trash to reclaim all of that precious hard drive space. Pro tip: Move it to your Finder Window's sidebar for easy drag-and-drop access.
AppZapper requies Tiger or Leopard and the $12.95US pricetag includes free upgrades for life. There are other apps that do this, yes, but AppZapper works perfectly for me.
Update: Some readers are reporting that AppZapper doesn't work properly under Leopard. It's never given me any trouble, but if you want an alternative, Hazel is a good one.