I find the discussion about "dead" areas interesting...I actually think it could be a valid approach to city placement. Fallen Enchantress did this, there were only certain areas could be settled. That made potential city spots extra valuable, as you couldn't just plop down cities anywhere (not until you got a powerful and expensive spell to revive land later on, at least). The uninhabited lands, meanwhile, would contain a mix of resources and dangers, which you would interact with through your armies or by building outposts.
I think a similar approach could work for civ as well, where not every position on the map could support a major city. This would mean fewer cities, but they would each have much higher value. City settling requirements could be eased with technological development, but the land would not have to be "dead" in the mean time. It could contain resources, outposts, villages, barbarians and so on, and the terrain would matter with regards to moving units through it. You would still be interacting with it, but in different ways than just filling it up with cities.
For most of human history (in game terms, until about the Renaissance Era and later) there were very specific requirements to place a city anywhere:
1. Water. As in Potable Water. ALL cities were next to a river, lake, oasis or other source of fresh water. There were no exceptions. As cities grew too large for local water sources, they either invested major resources in providing water (Assyria, Babylon and possibly Harappans all had 'aqueducts' or similar structures long before the Romans) or the city stopped growing. Major Drought lasting too long caused cities to be abandoned completely.
2. Food. Almost a no-brainer, but it means certain types of terrain, like deep desert or year-round frozen arctic that have neither access to water nor food sources cannot be settled by any concentration of people above a fishing village (arctic) or (very sparse) nomad group.
So, for about the first 1/3 to 1/2 of the game, there should be places on the map that simply will not support a city. BUT these same places will support some settlement below city level: hunting and fur-trapping camps in the arctic, fishing villages even on arctic shores, trade routes across deserts - and peoples native to most regions that are quite at home there, if thin on the ground. That means the game desperately needs a Sub-City Settlement of some kind - an 'Outpost' if you will - that allows you to exploit resources and perhaps claim territory, but does not have all the 'benefits' of a City - like Districts, Buildings, and Population Growth.
Suggestions:
1. No city can grow without Water access. IF there isn't an Oasis tile, river, lake, OR non-desert/tundra Mountain tile (because Mountains have streams running off them if there is any rain/precipitation at all in the region) in the city radius, then any city growth should be severely constrained - as in Impossible.
BUT from the Late Ancient Era, say about Tech: Masonry, you can 'invest' in a Water Supply System - a primitive aqueduct, basin, qanat system - to bring water from a source 1 - 3 tiles away to the city site. To make this a Non-Universal Solution, it might be tied to having a source of Stone available (and worked) to build your water courses, dams, basins, etc.
This would make it possible to build substantial (for the Era) early cities at Oasis, on the edge of Deserts or Tundra or other 'marginal' locations, but an entire Civilization of such cities would be near-impossible, as it should be.
2. ANY city with Sea Trade access and a Fresh Water supply - on a river leading to the sea, on the coast with Grasslands, Marsh or Floodplain tiles - has virtually no limits on growth, because food and any other requirements can be imported from the Ancient Era on by boat, canoe, raft, or (slightly later) sailing ship. This also gives Coastal Cities one of their Major Bonuses early in the game: less 'limits to growth' than almost any other city placement.
3. With Railroad connection, Any City almost anywhere has no limits to Growth: food and any other required Bulk Supplies can be brought almost any distance by rail in quantities simply impossible by any other kind of transportation. Consequently, placing railroads 'into the wilderness' turns the wilderness into a string of newly-valid City Sites. Look at the historical growth of cities in Siberia: as stated elsewhere, minor settlements until the railroad arrived, then major metropolises like Perm, Chelyabinsk, Irkutsk, etc. strung all the way from the Urals to Vladivostok along the railroad.
