"No Empire is a good thing, Captain." - Tamriel's Crisis of the Third Century

With Skyrim taking place at the very beginning of the Fourth Era's third century, and with the events that take place in Skyrim, a scenario similar to the historical Crisis of the Third Century seems likely. The Crisis was a chaotic period in Roman history, in which the Roman empire nearly collapsed due to a combination of foreign invasions and civil wars, including the formation of two breakaway empires: the Gallic Empire and the Palmyrene Empire.

With an emerging rift between the Colovians and Nibenese in Cyrodiil, Skyrim left paralysed by the Stormcloak Rebellion and High Rock isolated, witht the Breton petty kings left to their own devices, it's possble that in TES VI, the Empire will no longer be a cohesive political entity, but one riven by factionalism.

For example, let's say that following Titus Mede II.'s death, be it as a result of his assassination or just old age, the Elder Council installs a puppet on the Ruby Throne. The legions deployed along the southern border on the other hand proclaim their own emperor and capture the Imperial City, only for the Nibenese counties to rise in revolt, eventually forcing them to abandon it. Cyrodiil is effectively split between Colovia and Nibenay once more.

Meanwhile in High Rock, House Lariat - a powerful noble house who claim descent from the Septim Dynasty, proclaim the formation of the Bretic Empire and make war on the Imperial loyalists. Hammerfell, while still split between the Crown and Forebear factions, is potentially the strongest human political entity in Tamriel.

Sentinel, either on its own or at the head of a province-spanning military alliance, could intervene in the war in High Rock, perhaps leading to the formation of a Third Daggerfall Covenant, while the Colovian faction could try to restore the exiled Prince Dinahan to the throne of Rihad, of securing manpower and resources for the retaking of the Imperial City. Finally, you have Dragonstar, with its sizeable Nord population, likely emboldened by the on-going Stormcloak Rebellion, and Orsinium, which will no doubt have some problem with the local Redguards that could spiral into full-blown war.

The Thalmor of course won't stand idly by and watch all this unfold. The Renrija Krin could, on behalf of the Thalmor, be active in Hammerfell, making war on Redguard corsairs and trying to seize control of Hammerfell's criminal underworld. A network of agents and informers from the time of the Aldmeri occupation could also work to sabotage the alliance between the Forebears and Crowns. We also don't know if the Thalmor wanted southern Hammerfell just to control the Abecean Sea and drive a wedge between the Empire or Hammerfell, or if they had some other reason, perhaps tied to the prevalence of Dwarven ruins in the region.