Well, as you said, most large websites don't follow standard, so if you want a large website, you'd better not follow the standards. :)
But no, it's best to follow standards, because that will give you the biggest change that your site will function on most browsers, and will continue to function on most future browsers too for a very long time.
There are some exceptions, and they mainly occur because of some browsers (or some versions of browsers) not following standards. Therefor, you might sometimes need some tricks or hacks to get your site to function in all browsers you want to support. Most of these tricks can be applied while still following standards, but some others may lead to better performance or easier implementation or maintenance.
So while it's best to follow standards in general, there could always be one or two exceptions...
