So I decided to do this to get how major cities arise to some degree....

black is water, brown is road, dots are settlements.

Let's assume you start with settlement A and you are expanding out from there.
You're going to travel along the water and you are going to stop every 30km.
This creates a natural layout of settlements that will grow because why clear out a new area every time you travel?
MajorCityLocations.gif

From here Settlements B and C are going to arise as major population centers either due to being at the end of the fresh water which makes it a last stop which means people are going to want to prep and buy there which means it is a perfect place to have shops OR they are a settlement based around some resource. This puts them as more important that the settlements before.
MajorCityLocations2.gif

Next D and E are going to arise to import as cross roads between important settlements. F is going to arise very much the same way as A, B, and C, but it arises later due to Sea travel is going to be less important early on, but it will slowly gain more importance with it being the cross roads into that network and being just like A, B, and C being last stops.
MajorCityLocations3.gif

E may build into more importance, but roads built out from C (built because it is a shorter journey and managable to walk without much water) lowers E's importance while F being centralized and being funneled into by A, B, C, and D rather than C being funneled into D and then into E which makes it rise to be even more importance.
MajorCityLocations4.gif

As Sea and Ocean travel becomes more of a thing the importance of Settlement F increases and it starts controlling all in and outbound trade making it easily the more important city of the area and the connection with G across the water allows all that more trade funneled through F.
MajorCityLocations5.gif


side note: This uses a river to establish roads and that works from the base of a civilization, but as a civ grows settlements go into the land areas. The important thing to remember is that roads go between resources and take the shortest/easiest route stopping about every 30km (or maybe it was 50km). All settlements need a water source. Cities grow via trade, not because their land is good. If a settlement is at the cross roads of 4 cities, but on the worst land ever, as long as it can get water that city will become the most important of the 5 cities, because the central cross road city can live off the trade coming through it.