Fall of an Empire, Rise of Another (Main Quest)
This begins immediately after Layla returns to the Animus, following the events of The Last Medjay.
More boats, which means more ship combat.
The first wave is three triremes- standard tactics apply.
The next wave is fireships- they do massive damage on contact. Or so the legend goes- you can sink them with a single volley of arrows, so just take them out one by one, like headshotting zombies. Aim for the closest first, and you'll never get touched.
Next it's fireships and two triremes. The fireships don't damage the enemy, so cut across the fleet and mow them down, while using your catapults on the triremes whenever it recharges.
When the fireships are cleared, it's business as usual.
The last wave is two octoremes. The catapult does excessive damage against them, so use it as soon as possible, every time. Otherwise just try to use one as a shield against the other, and remember that they always fire in multiple volleys.
When they finally fall, the scene shifts to Rome. Show your commitment to stealth and invisibility by throwing down with Caesar's right hand man in the middle of the city, in broad daylight.
Septimius' close attacks have gotten stronger, and weirder, but otherwise he's much the same (if you do get caught in his bizarre tractor beam, mash the dodge button to escape). Unfortunately, Aya's lack of shield or longer melee weapons making getting past his morning star trickier. Start by using arrow attacks to boost your adrenaline meter.
The dual swords adrenaline attack remains as effective as ever- which is to say very effective. Always finish up the stabbing with an overpower attack as he stumbles backwards
When you run out of arrows, use the same overpower leaps to quickly get inside his guard after he finishes a charge. If things start to go badly, run and dodge while your health recovers. Eventually, he'll go down, and you'll be able to cross the last name off your list.
Now to Caesar- one giant yard full of soldiers lies between you and him.
You could kill them all, but if you want to commit to that whole stealth ideal, just scale the wall behind you, up until the spikes.
You can hand-over-hand across the entire level this way.
When you finally reach the other side, drop down and slip in the door.
Your most famous assassination will also be the easiest- just walk up to him and press 'E.'
The cutscenes that follow complete the main game
And also the quest Birth of the Creed, which apparently began and ended during these cutscenes.
You can now return to the open world. A new location has appeared in a Memphis- the Bureau of the Hidden Ones.
This place contains many scrolls hinting at subquests and secrets out in the world, as well as a special shop where you can buy Legendary Gear and trade drachmas for XP on essentially a one-to-one basis.