If you're running a program and dont optimize for every browser possible, you could potentially lose quite a bit of business.
For the companies I've done work for and the projects I have been on, we have to test every single browser there is and make sure they work properly. IE6, IE7, Opera, FireFox, Safari etc... that 2% of people that use the less common browser could end up being your bigest client/affiliate
Oh and the new Opera 9 now supports Ajax and CSS2 and then some...
