For either ES 5.5 or 6, I have some ideas:
1. It strikes me as a bit unbelievable that the Dwemer vanished. Consider: they were around when the Nords first invaded, kicked the Dragon Priests and Dragons in the teeth, and at the same time (it seems) were doing their best to make the Snow Elves extinct. Per the lore, the snow elves ran to the Dwarves/deep elves and asked for sanctuary, which was granted but in traitorous fashion thru enslavement.
Now if I was one of the Dwemer, I'd be viewing these Snow Elf - massacring and Dragon & Dragon Priest stomping Nords with trepidation. So: it would be logical for them to DIG DEEPER - go deeper underground and abandon their cities, which we explore as ruins. The Falmer wandering those ruins strike me as escaped slaves - notice how they are moving out of the Dwemer ruins and into caves and Nord ruins all across the map. It would seem a logical progression of the storyline if the Dwemer were actually safe within much deeper realms, their hordes of Falmer still enslaved except for the occasional escapee. Furthermore, one would think that the Dwemer would now be thinking that the Nords - embroiled in a civil war, under threat from the Thalmor and the Empire, fighting the Forsworn, their lands overrun with bandits, and now the Dragons wreaking havoc - were now extremely vulnerable.
Long story short - the Skyrim followup should see Dwarves emerging from the depths with hordes of Falmer and all sorts of wierd capabilities, ready to take Skyrim from the Nords. Their capabilities would have to be modified and enhanced - after all, a civilization that built all those robots and gear grinding machines and glowing lamps, still operating after thousands of years, can almost certainly make much better armor, weapons and metals than the junk they left hanging around in their abandoned cities (it really does strike me as bizarre that the Dwemer make the weakest collection of weapons and armor in the game.)
2. The dragons, after emerging from their long sleep, would be in a weakened condition, wouldn't they? The Skyrim successor needs to vamp them up, to turn them into real city-threatening terrors. Frankly, it should be impossible for a single character under level 30 or 40 to have any chance of slaying a dragon.
3. The Thalmor need to be explored and tested more. Consider: their strike against the empire seemed lightning swift and very successful, yet the lore says the Imperials took back their capital. The Thalmor also seem to be fanatically obsessed with the famous High Elf Slaying Talos. This suggests to me that their invasion, though tactically successful, was so costly to them that they are actually very vulnerable. Clearly they have no shortage of enemies, too - the Bosmer, for one. If I remember the lore correctly, it sounds like the Khaijit, Argonians, Redguard and Orcs have a beef with the Thalmor as well.
Something else: why wouldn't the Thalmor try to maximize the Empire's burden in Skyrim by providing support to factions like the Forsworn? It seems to me that the current storyline provides fantastic opportunities for political intrigue and asymmetric warfare for the Nords, Thalmor and Imperials.
4. Wars of the Gods. Example - Malog Bal and Boethiah clearly have a beef with each other. How about a war between the two? There's a LOT that could be explored with this concept.
5. Angry Daedra punishing recalcitrant champions. I have all the Daedra artifacts but don't use any of them. Why aren't they coming after me?
6. New, deep quest lines for the Thieve's Guild and Dark Brotherhood. There's just so many things that could be done - conflict between the two, a merger, conflict between their governing Daedra, all sorts of skullduggery involving Jarls, the Thalmor, the Empire, the Forsworn, danger from the Pentulus Oculatum acting as a kind of FBI, etc etc...........
Anyone else got ideas? Exploring these sorts of themes and ideas is tons of fun.