I want my game to be tricky and keep me busy all the way through, otherwise my empire will be at exponentially increased risk of collapse. Simply making the game harder all the way through isn't enough, and would only serve to kill off the human player towards the beginning, or simply make the campaign much longer.
My idea is that culture differences should fluctuate throughout the empire depending on its size and the region's importance inside said empire.
let's say you conquer Hispania, then 20 turns later you move just about all attention away from Iberia, because it's Roman now and All's Quiet on the Western Front, but then the Spaniards begin to feel like the shackles of Roman oppression are less visible to them, and their "Independent" factor begins to rise once more. This could happen many ways e.g. :
*** a rebel general spawns (random event) and is left too long spreading anti-roman sentiments, thus spawning more rebels, and eventually a formal rebellion force. Here I differ between the grey army of nobody's faction and an actual uprising of the previously defeated faction, respectively.
*** the building/development regime has left the province and the inhabitants feel neglected.
*** the region is on the frontier and culture transmission affects the populous.
...The above events can (and should) avalanche into a tidal wave effect unless stopped immediately. A single region would affect the rest of the regions in the province, and once a province is lost, the surrounding provinces begin their own destabalising processes.
You can see how this would be a great REALISTIC mechanic for a completely natural Barbarian Invasion event.
By the time the Empire grows to such a size that it seems the player cannot lose (the practical size of the historical Roman Empire around the time of Hadrian, let's say), then huge areas of the empire would be left undefended (unless every region is heavily garrisoned - which simple faction economics could keep in check), and the above events would be much more likely to occur, thus destabalising the entire empire. Even if the player can manage to settle these revolts, then the external factions outside the Empire would see this as a weakness in the Roman Empire, and be more inclined to attack en masse.