The most popular one is http://www.gamesas.com/index.php?/topic/1100516-relz-fwe-fo3-wanderers-edition-40/(FWE), but I personally prefer http://www.gamesas.com/index.php?/topic/1096923-relz-arwens-realism-tweaks-thread-no8/, along with other mods that she recommends on http://amito.freehostia.com/Fallout/FO-mods.htm, like real injuries/primary needs.
Very challenging indeed.
Arwen's does not add any new content to the game like weapons or armor or anything, it's purely gameplay tweaks. FWE adds a whole lot. It all comes down to what you're looking for. Both mods also attempt to achieve realism and better difficulty in different ways.