Alta´r's lengthy rant into the nature of religion seems to be the game lecturing the player about the irrationality of it all and how death ends life forever. This, despite the fact that All Myths Are True and a form of scientific reincarnation exists with genetic memory. It's quite likely that other myths are true in a scientific way as well. It's further undermined by the fact that the destruction of religion is the stated goal of the Templars, the people Alta´r is fighting. Then you remember that Alta´r is in control of the Apple of Knowledge and the thing has a One Ring-like effect on people's minds.
It helps to understand Alta´r may also believe that while All Myths Are True, the nature of the truth invalidates any religious truth from the stories. Likewise, he may just object to the methods of the Templars as opposed to their goals.
One of Alta´r's victims back in 1, Sibrand, also saw through the Piece of Eden and found oblivion in lieu of an afterlife.
You have to wonder why Ezio and his brother move like champion acrobats and Le Parkour masters even before they've had any assassin training. Then, duh, of course, you remember that they're children of an assassin. Simultaneously, it might be In the Blood as well as their father preparing them in subtle ways for their life ahead.
It's also likely that they learned from friends and through dicking around in Florence. Apparently, if we're to believe the heralds it's become quite popular with the young men to run and jump on top of the roofs in Florence.
It's actually implied/mentioned that Federico had been learning at least some Assassin skills from his father, presumably preparing them for induction into the family business (Federico has to be doing SOMETHING all day, and in his Codex entry it's said he no longer works at the bank after a Noodle Incident). He then passed them on to Ezio and Śin what might be a way to help keep the heat off the Assassins in FlorenceŚ other young men as well.
In one of the earlier cut-scenes, we see Ezio's dad fully accepting Ezio's trouble with the law / escapades with women. He says it's because it reminds him of himself, but maybe he WANTS him to crawl around the city, fleeing guards.
Desmond doesn't have to be a direct line of descent. As the child of Assassins, it's quite likely that their various families intermarry. Desmond's Ambiguously Brown features help this as well.
Even before the retcon in Brotherhood, Ezio's shrugging off Rodrigo's gut-stab is foreshadowed by Alta´r doing the same thing early in the first game. And also inflicted by the Big Bad, though you don't know it at the time. Coincidence or Call Back?
The strongest set of equipment you obtain in Brotherhood is the armor and dagger of Brutus, which you will likely use against Cesare. Think about that for a second.
The reason that no one seems to age over the past twenty years. Remember that we're experiencing things as Ezio remembers them. Most likely Ezio just always remembers them looking the same regardless of age. His sister always looks 15 because in his eyes, she's always been his little sister.