The City of St. Louis is a separate entity from St. Louis county. When I last checked the employee map for a 150 engineer software company, there were two employees living in the City of St. Louis, (a receptionist, and a newly divorced man in an apartment) the remainder where in St. Louis County, St. Charles County, and living on the "east side" in Illinois (but far enough to clear East St. Louis).
The City of St. Louis has a 1% payroll tax for people that work in the city, plus another 1% for people that live in the city. That may not be important for a startup, but if you are looking to long term employ a lot of highly paid people you have to ask yourself if you want an extra 2% margin or not.
There has been a fair amount of redevelopment in the city itself in recent years, and probably a large amount to come, so you can find a nice place. Make sure to check for a grocery store nearby. Public transit is next to useless. Prepare to drive.
The radial highways in and out of the city are in pretty good shape these days. Check the actually commute times, but 20 miles in 30 minutes wouldn't be outrageous.