In Morrowind, it was possible to permanently kill NPCs who were involved in the main story. This would result in a message basically informing you that you had broken the world and to reload a save if you want to make progress. In Oblivion, this was changed so that important NPCs were "knocked out" instead of killed.
In Skyrim, is there any (outside of console or game file editing) way to permanently kill an important NPC or can I go on a killing spree relatively care free?