Although in the past it has not always been the case, these days you must test your sites against multiple browsers for compatibility and proper rendering. At a bare minimum my test are against IE 7, IE 6, FireFox 2, Safari (windows), soon to be IE 8 🙁 and sometimes Opera. If you can test against all of these and your site still looks and works right I would say you have covered your bases pretty well. That may not be the best way, but again in my experience that covers 98% of who will visit your site. One issue you will run into almost immediately is how to test your site against multiple versions of Internet Explorer on the same machine. Microsoft offers a Virtual Pc (Free) image that is made expressly for this reason. All you need to do is download it and mount the image and you are testing!