Depends on the audience.
If you're Amazon.com, Ebay or Google, you're probably going to have to support every browser under the sun except perhaps Netscape 4.7 on Intel Solaris (Note I have actually used this combination while I did my B.Sc, but that was more than a decade ago).
If you're aiming at a broad web audience, IE7+, FF, Safari, Chrome and maybe Opera
If you're expecting users on corporate intranets, you may well have to support IE6+.
If you're aiming at mobile users, Opera and various mobile browsers.
