-This game takes place in 15th century Italy, rather than the 12th century Holy Land.
-We have a new player character named Ezio, who was a member of an important family in Italy, now out for revenge for an undisclosed reason (but I think we can all hazard a rough guess)
-Ezio can swim (as he damned well better in Venice)-
There is much greater weapon variety (more on that later)
-There is also much greater side mission variety (again, more on that later),
-Rather than just taking place in Venice, this game will also take place in Florence (possibly other cities as well, those are just the only confirmed).
-There will be countryside like in the first game, however there will actually be missions to do there, and it won't seem like the cities are the only civilization.
-Bales of hay make a return, but they are no longer the only viable hiding place. You can now blend in with entire crowds, rather than just with monks, as well as in the water (water can also serve in the same function as hay, cushioning a fall) so long as Ezio's breath holds. You can also stage assassination on nearby guards while hidden (for example, pulling a guard into your hay bale and stabbing him)
-"Safe spots" are no longer all that safe. Enemies with pikes and halberds can and will stab hiding places they suspect you to be in.
-There are a great many weapons, but you take them all from enemies. The only weapons you will carry permanently are throwing knives and your hidden blades (yes, that's plural). As such, the unarmed fighting has been revamped with a Disarm move, but Ubisoft has commented that eventually, players are just going to use their hidden blades and not bother with weapons. Creative Director Patrice Desilets commented "If you're really good, I'm hoping that you're mostly fighting with the hidden blades. That's the goal. At the end, you're just a bad-ass assassin, without needing all the weapons."
-Leonardo Da Vinci, Machiavelli, Caterina Sforza, and Lorenzo de Medici are all confirmed to have appearances, with at least Da Vinci playing a major roll.
-Ezio has a reputation. The more assassinations and such that you do, the greater your notoriety. When your notoriety is high, guards are more wary , but you can perform certain missions (such as tearing down wanted posters, bribing those who are talking about you, assassinating witnesses, etc) to get it low again.
-Side missions have been completely revamped. There are apparently 200 missions which can be sorted into 16 categories. However, according to the article, just because there are general categories does not mean that one mission will repeat another. After the article mentioned that Unisoft knew our complaints, Desilets commented "We thought, let's forget entirely about the idea of a really strict mission design concept. There's no preset structure." Also, apparently missions might happen back-to-back, for example, Desilets commented "So you start doing a delivery, and that transforms into a chase, then you end up with a killing mission." A specific example of a single mission provided by the article was "Ezio heads to a nearby palace where a noblewoman holds some vital clue. Upon arriving, she informs him that she is in grave danger, and he must defend her from assassination as they flee through the streets. Reaching a dock along the Venetian canals, they escape by boat, and Ezio must keep the craft afloat until they reach safety."
-There is apparently also more enemy variety. For example, you have your standard mooks, like the first game, but you also have elite mooks who, although only armed with a knife, can follow you on the rooftops, and another type that, although they can't follow you, are very heavily armed and armored.
-There is a night and day cycle.
-Collectibles will serve a purpose other than achievements. The article was tight-lipped on what gameplay purpose they serve, but they mentioned flags, statues and coins, so maybe we can finally give coins to the beggars so they leave us alone.
-In order to make the experience flow, good parkour paths are marked with white sheets.
-New climbing moves have been added. "...the climbing system has been reworked with a new leap and grab maneuver that allows easy traversal of seemingly sheer vertical surfaces."
-A mission wherein you must get into an enemy stronghold with Leonardo's glider. This happens at night, apparently, and your allies light fires on the ground on the way to give you enough updrafts to make it.