This text explains the differences, at least for the Vampire side of things: For starters Generations are now gone vampires no longer belong to a generation and instead a system called Blood Potency is in place of that as a vampire gets older their Blood becomes more potent making them more powerful. However xp can be spent to increase Potency as well meaning some very young vampires can become just as powerful as a Elder, though when it comes to me I usually ask for some story based explanation of why the young vampire is gaining more potent blood (did recent events have some strange or mystical effect on them? Why is it?). The potency of their blood also effects who and what they can feed on thus the older they get the smaller their pool of prey becomes eventually making it appealing to enter Torpor and sleep away the decades or centuries as Torpor will cause their Blood to loose potency. The Mythos of Vampire the Masquerade involved the legacy of Cain from the Catholic/Christian bible and it's worth noting the nWoD Vampire the Requiem no longer has anything to do with this and instead establishes it's own mythos and lore which I'll explain further below after I get into the covenants since the covenants are what establishes the new mythos. The Camerilla, Sabbat, and Anarches do not exist in New WoD's Vampire as the Camerilla fell with the fall of Ancient Rome in the nWoD history and instead these groups are replaced by the system of covenants made to fill certain aspects and roles those groups filled as well as ones they didn't. The prince of a City no longer need be tied to a specific covenant to be prince either they can be completely unaligned or they can belong to any one of the covenants this makes the politics of the game's covenants more interesting as each vias for power so they can be in a position to take over should the prince fall. the Existing covenants are as follows, the Invictus fills the slot of aristocratic kindred (vampires) that the Camerilla once was all kindred with power and wealth in a feudal hierarchy. The Lancea Sanctum is a covenant which fills the role of providing a religion and Catholic styled mythos to the game a cathloic church type mythos to the game taking considerably from the Catholic Church in how the covenant is structured and how they do things. The Lancea Sanctum preaches Longinous, the roman soldier who pierced Christ's side with a spear while he was on the Cross was cursed by god to be a vampire and in being cursed was also given a task by god thus becoming a Dark Prophet for the Kindred. However the Lancea Sanctum is not the only source of Religion for kindred, the Circle of the Crone is a covenant that provides religion for and religious mythos for the kindred in the game and it's focus is on pagan beliefs such as the anicent Greek or Eygptian deities. The circle of the Crone is a loose coalition of different cults all worshiping different pagan gods and goddesses of every ancient religion you can think of. In any city there might be one to a half a dozen different Cults all belonging to the Circle of the Crone. It's also worth noting that both the Lancea Sanctum and the Circle of the Crone have Blood Sorcerary however each covenant's blood sorcerary is different both in theme and slightly in how it is used, but both thus fill the slot left open in the removal of the Tremere clan from Vampire. Belials Brood is a covenant that fills part of the role left open by the removal of the Sabbat, and the VII covenant fills the other Part of the Sabbat's role. other covenants in the game with roles which fill some what new niches are the Ordo Dracul and the Carthians, and that I believe just leaves the Unaligned which basicly fill the role of the Anarches. TL;DR? The story is way different, it uses other mechanics instead of Generation, and the clans are weird, in my opinion.
