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There are new icons for the "like"/"dislike" buttons, there's a new way to show the navigation sidebar and the "more from" section has been removed.
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The homepage looks a lot different if you're not signed in. YouTube shows popular videos from topics like entertainment, sports, news, movies. The topic pages areautomatically generated by YouTube.
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You can check some screenshots from the previous YouTube experiment.
Here's how you can try the new interface. If you use Chrome, Firefox, Opera, Safari or Internet Explorer 8+:
1. open youtube.com in a new tab
2. load your browser's developer console:
* Chrome - press Ctrl+Shift+J for Windows/Linux/ChromeOS or Command-Option-J for Mac
* Firefox - press Ctrl+Shift+K for Windows/Linux or Command-Option-K for Mac
* Opera - press Ctrl+Shift+I for Windows/Linux or Command-Option-I for Mac, then click "Console"
* Safari - check this article
* Internet Explorer - press F12 and select the "Console" tab.
3. paste the following code which changes a YouTube cookie:
document.cookie="VISITOR_INFO1_LIVE=jZNC3DCddAk; path=/; domain=.youtube.com";window.location.reload();
4. press Enter and close the console.
Update (December 7, 2012): The new interface is available for everyone and you can no longer go back to the old layout.
{ Thanks, Abhishek and Lukáš. }