A combination of many Fallout 3 mods that together increase the challenge, sense of immersion, and depth and breadth of options of the original game. You'll find the wasteland a more dynamic and far less forgiving place.
For a while, I steered clear of the bigger gameplay overhauls for Oblivion and Fallout, unsure of what kinda chaos they might wreak. I did, however, have gobs of mods for each- very little of my FO3 main character's equipment was vanilla hardware, and I did indeed have a plethora of gameplay mods. It got quite unstable, all those plugins fighting each other for supremacy, and the crashes chased me away from the game for a while.
After some thought, I decided to give the well-acclaimed FWE a try by starting some new characters, and I am very glad I did. Many of the features I used to have a stack of mods for are all rolled into one with FWE. Things work much better now, and due to its popularity, many other plugins are made with FWE in mind, so compatibility is no sweat.
This is the game Bethesda should have given us. Survival is now the challenge it should be in a post-apocalyptic world. Ammo, chems and caps are rarer, healing is no longer as simple as spamming stimpaks, and food, water, and sleep are now truly vital. Combat is now a brutal affair- increased global damage and reduced player health mean a lot more ducking and covering, and oftentimes a lot more pain.
If you've played Fallout 3 to death, and are looking to refresh the Wasteland experience, I'd gladly recommend Fallout Wanderer's Edition.