Castel Sant'Angelo
The Castel Sant'Angelo was a significant, cylindrical fortress located on the northwestern edge of Rome during the Renaissance period. An end point to the Passetto di Borgo, Ezio Auditore da Firenze scaled the Castel Sant'Angelo in 1499 during his infiltration of the Sistine Chapel. It is the highest View Point of any Assassin's Creed game.
Liberation of Rome
The Castel is the most heavily guarded building in Rome. It was guarded by Lucrezia Borgia for at least awhile, before Ezio infiltrated it to assassinate Cesare and Rodrigo Borgia. However, both of the Templar leaders left or disappeared before Ezio could kill them. Ezio successfully rescued Caterina Sforza. Later, in 1503, Ezio once again infiltrated the Castel. At a window along the wall of the fortress, he witnessed the murder of Rodrigo Borgia at the hands of Cesare. Ezio also found out the location of the Apple of Eden, thanks to Lucrezia. [1]
Glyph
One of Subject 16's coordinates is located here. Jump across the beams in the water (the same way you go in the mission to rescue Caterina). Once you reach the first group of guards climb up the ladder and then up the wall to your right (again the same route from the mission). Head left on the walkway towards the hay. Jump to the tower directly across from you, there should be a round window. Use eagle vision and the glyph should be just below you. Drop down, catch it, and enter.
Achievement
The achievement Fly Like An Eagle can be earned when Ezio jumps with the parachute off the top of the Castel (the flagpole).