Major cities like LA, SF, NYC and others are overdeveloped, overpriced, crawling with rootless international types with ties to the city other than owning real estate. Everyone knows about Austin and Portland but even those are getting a little too overdeveloped and played out.
The real sweet spot are places like Salt Lake City, Nashville, Milwaukee, Kansas City, Raleigh, etc. These are places where housing costs are extremely low, culture is thriving and the economy is decent.
Given the homogenizatoin of yuppie professional culture (in terms of clothing, restaurants, amenities, transportating, housing), there's really no reason to live in a big 1st tier city unless you're from there or you're really making a lot of money. But even then, I usually have more fun in the other cities.