I think a medium sized city is probably the best balance between the rat-race, high prices, and traffic jams of the large booming economy cities and the picturesque, charming, laid back small towns that offer very limited employment opportunities.
I spend a good bit of time living between Charlotte & Boone, NC. I also have family in Atlanta, which dwarfs Charlotte. From what I can see the people in the medium sized cities usually have most of the benefits of the larger cities without the costs & the stress. They usually have an adequate job base, convenient shopping, and affordable real estate.
I think the main drawback of many medium sized cities is that they aren't usually as politically progressive as larger cities and small college towns usually are. That can be difficult for many people that are used to living in a more culturally divers and open-minded city. Personally, I don't mind voicing my opinion about things, but I don't live and work in a medium size conservative city, so I can't "really" say how I'd fit in.
Something I've noticed from living in Boone is there are the "locals" and everybody else. The locals have been there for generations, they all know each other, their families all live nearby, and they are all Baptist. If you move there from somewhere else you'll "never" be a local, and your children that are born there won't really be locals either until they actually get married, have kids, attend church, and the kids are in school.
I'm not saying the locals aren't friendly to outsiders, because they are, but there's just a cultural identity that takes generations & years to join. I've found it very entertaining to try to learn some of the local gossip. Many of them love to chat and fill you in on the local history, which is endless. A writer could fill volumes living up here.