Last night, YouTube launched a new design for the site - it is a pretty significant change.
The main thing you will notice is that the videos are much higher on the page. It takes up more space horizontally and adds various navigation to encourage you to watch more videos.
Here is a screen shot:

So what has changed? Here is an outline but if you want all the details, see this YouTube Help thread:
- Home Page
-- Account Links
-- Feed Views
-- Subscriptions
-- Subscription Options
-- Your Feed
- Managing Your Subscriptions
-- Bulk Edit
- Video pages
-- Video at the top
-- Information, subscribe button, sharing options and more at the bottom
-- Playlist appears to the right of the player
YouTuber wants your feedback and they posted details on how to provide that feedback in the YouTube Help forums.
Forum discussion at YouTube Help.

Comments:
@dan_m777
12/07/2012 01:16 pm
The first issue i noticed was that there was a massive white space on the right.
ethalon
12/07/2012 01:18 pm
I had been seeing this design popping up every now and then for quite some time now. I was wondering when they were going to roll it out. I am not a huge fan, but then again it is something new and I find my reaction to new layout changes always take a little while to get used to. I will reserve my judgement until I have had some more time to interact with the interface.
Andy
12/07/2012 01:25 pm
Yeah what's with that? It's a complete waste. To make it look nice they could have at least centered it...
tecnonetblog
12/07/2012 04:39 pm
First experiment in the new YouTube interface: http://tecno-net.blogspot.com/2012/12/first-experiment-new-youtube-interface.html
Nikolas
12/07/2012 05:12 pm
Now one can't search for most viewed today, whats up with that? That's the only one i really use. Big mistake removing that
Sam
12/07/2012 06:22 pm
you can still see popular videos, youtube.com/charts
Alex
12/08/2012 09:35 am
You can not select most viewed anymore for a search conducted, I am really pisted off by this!