For those of you wanting additional challenge, Darksiders II will feature a Hardcore Difficulty which will unlock once you finish the main game. In this mode players have one life and if they lose it via a combat death they lose all saves associated with that playthrough and will have to start from scratch. This is a truly apocalyptic challenge for only the most skilled horsemen!
Keep in mind again that your save file is only reset if you die in combat, so things like falling deaths or getting killed by lava are not things that will reset your gameplay within Nightmare mode.
Interesting. I'm curious if playing through the game multiple times will result in better loot so you could eventually get through this more easily.