After having read it it seems kind of obvious but I had to make a note here. I think it’s a brilliant insight and although many designers have embraced this—dropping IE—for their blog designs, it’s a move that hasn’t been taken up yet elsewhere:
Yes, none of this stuff works in IE, and IE still has massive market share — but not among the sort of people who adopt hip new web apps. The combined market share for, say, Firefox 3 and Safari 3 is larger than the overall market share for Mac OS X. Plenty of developers write desktop software that only works on the Mac — why aren’t more people writing web apps that only work in truly modern web browsers? The first one to do it is going to be a sensation.—WWDC 2008 Miscellany
(emphasis mine)