The Nightmare, Hell and Inferno difficulty modes have been replaced by a new dynamic difficulty system, which itself is divided into subcategories: Normal, Hard, Expert, Master and Torment, with the latter being further divided into six gradations. New social features include Clans and Communities, which give players access to private member rosters, news and info postings, and dedicated chat.
On top of all this are loads of character-specific updates, boss and monster tweaks, new stats for heroes and more than we could possibly squeeze into this post. For every little detail, you can peruse the patch notes, and Blizzard's official online Diablo 3 guide has also been updated to walk players through all the changes.
Oh, and don't forget that there's one huge change that's still to come: The auction house is closing on March 18.