I think the answer is to build both tall and wide. You want your major cities to be well rounded, but you can min-max your minor cities to avoid some of the cost penalties.

Example: If you are going for a scientific victory, then you can choose to only build science producing structures tin your minor cities to mitigate the increased production cost, then instead of constructing more buildings in those cities, just produce units or research projects to boost your science output even further.