I have long been of the opinion that sometime in the next 5-10 years, it would be in the best interests of both our team and C2C itself to start making plans for a solo game built from scratch, which I would suggest should be a non-commercial simulation/grand strategy hybrid that plays like a cross between Civilization II, III, IV, Galactic Civilizations (plus Final Frontier and its descendants) and the Paradox grand strategy game series (particularly the Crusader Kings->Europa Universalis->Victoria->Hearts of Iron metaseries). Even if we leave aside questions of legality, the amount of work it would take to convert a 32-bit 2005 (well, a few years later if you go with BtS and the last patch, but still around a decade or more) game into a 64-bit game would, if anything, be more work than creating our own.
Sadly, the AXXXXXE project seems to be inactive, but that's no reason we can't brainstorm. I think a critical element of managing truly massive (like, Galactic Civilizations III's latest big map settings, which exceed the largest Civ IV (let alone the post-decline games) maps to a greater extent than those maps exceed Duel) would be some ability to designate, in a manner similar to custom fiefdoms in Crusader Kings II, multiply nested and overlapping administrative divisions, so that you could depict polities on the scale of the People's Republic of China or The Gambia with comparable alacrity. I also think another thing Paradox games have over Civ is their depiction of provincial-type units as the smallest administrative unit for a polity: imagine both in real life and game terms what a nightmare it would be if, say, a polity's head of state had to micromanage the affairs of every single municipality.
There's also the fact a lot of the things we currently require player input for in C2C are things that wouldn't always be organized by the central government in all but the most centrally planned of economies. A rough equivalent to this in current-Civ that would provide a useful analogy for any independent sequel plans would be that if your city possesses the requirements for a particular building, that the building isn't on a series of special lists (not a wonder of any kind, not a non-state religion under a non-tolerant religious civic, not an economic building under a civic where it wouldn't make sense (Stock Exchange under the Planned economic civic, for example, not a major league NIMBY (to take a couple of quite different examples, anything associated with nuclear technology or sanctioned criminal buildings), the list probably goes on for some time but you get the picture, that building is automatically built by your citizens. This would vastly reduce the load upon players currently satiated with building lists, which is one of the reasons I would make it possible for the player to manually delegate that sort of authority even if they use a highly centralized, highly planned set of civics.
I think there may be merit in differently-sized and shaped tiles as well, but you'd have to be careful that scale remains consistent, and in order to have that you'd need some kind of base constituent unit, even if it remains inaccessible to the player's viewing, so my current idea is to bite the bullet and go for Earth-sized maps (with precision options to go lower for players who prefer it that way or have older or slower computers) with each tile representing 1000 square kilometres (which would give roughly 510,000 tiles, comparable (give or take a few ten thousand, IIRC) to the current largest map for Galactic Civilizations III, which is designed for 64-bit systems and that map size's recommended RAM is 32 GB.
Space maps are trickier, but we could take an idea from Aurora 4X, which I haven't played but I gather uses some kind of system with partial procedural generation to allow accurate maps of entire solar systems. The most critical elements are going to be the planets, their satellites (natural or otherwise; the term in astronomy describes both Luna and Sputnik), and any units; you could probably incorporate a Homeworld-esque 3D fleet command system in a similar way to how some have suggested tactical battlefield maps for C2C in Civ (reminds me a bit of the Total War series, actually).
Oddly, things get both easier and harder when you get to higher level space: easier because there's little to account for but solar systems, planets and units, harder because of the sheer magnitude of the numbers involved. I'm of the rare view that most science fiction could be set within a few hundred star systems, if not anywhere down to a single solar system, with little need for change, and even the technologies of the Transcendent era need not be accompanied by a comparable increase in the scale of civilization: there's a difference between having a Theory of Everything and access to higher dimensional manifolds and actually sending people/posthumans/whatever out to colonize these things. What in this case I think really matters is not what you call your map (galaxy, galaxy cluster, supercluster complex, observable universe) but how many tiles it has and what your player has to deal with: from a strictly gameplay perspective there is little to no real difference between a microgalaxy and a map encompassing tens of thousands of stars within some subsubsub (insert or subtract for accuracy) region of a normal sized galaxy.
There's another point I'd like to make on the note of eras: some of this could be achieved in C2C (even if in rather unorthodox ways: I've been thinking for a while we should look into the code used in Fall from Heaven: Age of Ice and repurpose it to model ice ages both Paleolithic and global warming related), but either way, I'd like to mention it: I think I would have as the first era, the Paleolithic, which would overlap with most of what C2C currently calls Prehistoric, as being very different in terms of lore, gameplay, and how to exit it. Basically, in lore terms, you control the patriarch of a band of Homo sapiens sapiens, living a nomadic, hunter-gatherer lifestyle. This would have much in common with the Nomadic Start, and it would be less like playing a sedentary era with different tech and units, and more like a different game altogether (the plans for that great tragedy of the late 2000s, Spore, come to mind). There wouldn't really be a tech tree in the normal sense: there would be technologies you can unlock, but they'd be more akin to the ones in Factorio or the survival genre (whose popularity I think owes itself to its similarity of its setting to that of the majority of human evolutionary history), and your basic goal would be to survive the harsh, unforgiving natural world and slowly accrete human capital until you reach a threshold where you can outlast the ice age and learn how to farm.
I have tentative ideas in the direction of changing how eras progress in other areas too (there would likely be the possibility of skipping eras under the right circumstances, some of which would overlap with alt-timeline stuff: industrial revolutions of a Sandalpunk nature, for example), but if any era deserves to be given special treatment in this regard, it's the Paleolithic: even Transcendant has more in common gameplay-wise with the Neolithic. It is incredibly difficult to express how alien the world of that era would be to modern society: there are almost no cultures in recorded history that could be described as Paleolithic, even among uncontacted peoples. Possible exceptions include the Australian Aborigines (I read an article yesterday telling the amazing story of an uncontacted Aboriginal group, which first showed up on the radar of civilization in 1988), some Papuans (believed to be genetically and phenotypically similar to Aborigines) Native Americans from the Pacific Northwest, and the Khoisan/Bushmen of southwestern Africa (though I read their lifestyle is a deliberate choice (I'd guess environment has something to do with it), they could go Neolithic but choose not to.