Bethesda Cranks Up Fallout 4 Survival Difficulty With 1.5 Beta
One of the primary things Bethesda focused on when developing the new Survival Mode was it "wanted to force you to make interesting choices." To that end, gamers will have to put more thought into when to fight and when to avoid combat, along with what gear to take, and then "back up those decisions with faster, more brutal fights."

Fast Travel is gone in the new Survival Mode, a feature removal that's already irritating some players who point out that it's a pain in the backside to truck it across the Commonwealth whenever their settlements are attacked. That wasn't necessarily Bethesda's intent—the developer wants to encourage exploration.
Bethesda also removed the ability to save a game on a whim. Manual, quicksaves, and nearly all autosaves are disabled in Survival Mode. If you want to save, you'll need to find a bed and sleep for at least an hour.
"This means your fallback options are reduced, forcing you to be more concerned about what you are walking into an whether you're prepared to handle it," Bethesda says. "Some fights you may deem above your level and decide to avoid. Other fights you may decide to go all in."

You'll dole out and take more damage in Survival Mode, which makes combat more dangerous and increases the importance of having a strategy. And for melee players, it means the need to use block/parry. Bethesda is rather unapologetic about about the increased skill that's required, noting that "those who opt into Survival know what they're getting into."
There are many other aspects to Survival Mode designed to make it a brutal experience, things such as illnesses, immunodeficiency, slower healing, crippled limbs that no longer auto-heal after combat, and a reduction in total carry weight, to name a few.