"The Midwest of the U.S."

Solution 1:

The difference between northeast Baltimore and Middle America is that "Middle America" is the name of a particular notion that has extra connotations outside of just the fact that it is in the middle of America. As you can see, it carries with it the concept of the middle class and conservative ideas. So, this whole phrase is the name of a thing that is greater than the sum of its parts, and it is capitalized. The northeast of Baltimore, on the other hand, is not the name of a specific region in the sense of being defined and carrying any extra meaning.

This happens all over the place. If I talk about living in east St. Louis (and the reader knows I am not being careless in my capitalization), then they would assume I probably mean the eastern region of the city of St. Louis. But if I say I live in East St. Louis, then they know that is the name of a different town located next to St. Louis, in a different state.

Solution 2:

Midwest is a proper noun in that context, so it must be capitalized. Unlike northeast, it is not a standard direction; it is referring to a specific region of the U.S.

Northeast is both a direction and a region. When it is a direction, it is not capitalized unless it is used as part of a proper name.

Middle America is a proper name, thus both words are capitalized. The middle of America would not be capitalized.