What browser support matrix do you use? By this I mean which browsers do you insure pixel-perfection in, which ones do you support functionally but not visually, and which do you not support at all?
At the moment, I aim for pixel perfection in the following:
Webkit:
Safari (latest)
Konqueror (latest)
Google Chrome (latest)
Gecko:
Firefox 3.x (latest)
Netscape 9 (latest)
IE:
IE6
IE7
IE8
EDIT: I forgot Opera! Full support in latest version of Opera is a must, being in Norway and all=)
Why only the latest versions? Because people who use these browsers are pople who know what a browser is and tend to update them. Most companies I have contracted for support Firefox 2.0, but of the about 200 000 firefox users that have visited (my company's) website this year, none used Firefox 2.0, so I have decided to drop it. I test in XP and on mac.
A quarter of our site's user use IE6. It makes me want to cry but there's nothing I can do about it.
We have had visitors using IE5.0, IE5.5 and Netscape 4. Too bad. They're on their own. (The site actualy looks rather good in IE5.0. But I'm not gonna check from now on. Unless I'm feeling curious.)

