I've had an idea for a tl following the development of a hypothetical city on the Mississippi called Rome. It would be on the Kentucky shoreline. However, I need to know whether it would be plausible for a city could have been formed by the Order of Cincinnatus in this area. I also need to know whether this city could have evolved into a whiskey trade based city, and how large a combined machine tools, whiskey and steel based city could grow too. How about if they added automobiles and agriculture to the mix.
I'm afraid a major city in the Jackson Purchase area wouldn't be terribly likely, TBH: not a lot of good land there.
If you wanted to try it, St. Genevieve, Mo., had some promise; maybe not as a rival to STL but it could've still been something-same could be true for Kaskaskia, Ill., too, as other have mentioned.
There's also the Quad Cities-Rock Island and Moline, Ill., were especially good places for a city, but Davenport and Bettendorf in Iowa, as well.
You could even try for Baton Rouge in Louisiana, though it might have to involve a major disaster in New Orleans(Katrina 200 years early?).
To those wondering why Cairo, Illinois never developed - a combination of horrific racial strife and being devastated regularly by floods and tornadoes of a biblical scale.
Not to mention the geography-the city is actually rather narrow, on a peninsula only around 10 sq. mi., last I checked.