Cool HTML5 and CSS design kung fu in Chrome, Firefox and Safari more often than not fails on Internet Explorer.
Microsoft's response? Fuck off. We own the browser market. Deal with it.
But as mobile web apps rise in prominence, some devs are starting to push back: 4ormat just dropped IE from its support matrix. Not only do I agree, I encourage more designers to advocate this. It saves time, saves money and saves headache.
Even if you have to support IE, just detect the browser to add a note at the top of your page saying, "This web site looks better in Chrome, Firefox and Safari. Isn't it time to upgrade your browser?"
Microsoft, your browsers are pooping on good user experience. Wake up!