New information revealed (with some very minor spoilers):
*The Brotherhood of Steel is back, but the core story revolves around the NCR and Caesar's Legion.
*SPECIAL now has descriptions - eg CHA 10 = Cult Leader, EN 1 = Basically Dead.
(Those descriptions for Strength: 10 - Hercules' Bigger Cousin 9 - Doomsday Pecs 8 - Circus Strongman 7 - Beach Bully 6 - Barrel Chested 5 - Average Joe 4 - Lightweight 3 - Doughy Baby 2 - Beached Jellyfish 1 - Wet Noodle)
*You get a Vault 21 jumpsuit from the doc who revives you, along with a pistol and a Pip Boy 3000.
*Weapons can be modified, but modifications only have positive results. The magazine implies you won't need to make a choice between different mods, because they won't be mutually exclusive.
(And a little later the magazine contradicts itself by writing that adding a larger magazine increases reload times.)
*Every weapon has a special attack, not just the golf club. It seems that Fore! does not mean groin shots are back for every weapon.
*Guns have different knockback amounts, pistols don't do much, shotguns blast people away.
*There's a town-specific reputation, and Obsidian has 'hinted' that the reputation will impact endings.
*Karma has been overhauled, tracking the factions and ideologies that you agree with.
*Nightkin are back, as blue-skinned Super Mutants who've gone schizophrenic through Stealth Boy use. They attack you while cloaked, deactivating cloak at the last minute to hit you with a club.
*The Tabitha situation can also be resolved by convincing Tabitha to revolt against the other Super Mutants.
*Helios One is not only a power plant, but also the location of the controls of a solar weapon developed by Poseidon Energy which you can employ yourself.