Major as downtown area of 7 million+ metro, Some of these may be obvious, so bear with me. Just my two cents:
1. Cost of living: Night and Day. I rent a nice-ish 2 bedroom house with nice trimmings (granite counter top, washer/dryer, .5 acres of land lots of space) for $400/month. I can get all my groceries for the week for less than $75. Beer is cheaper. Everything is CHEAP. You can actually live on 50k here. I made 80k in the big city and lived paycheck to paycheck.
2. Food. This has been the biggest adjustment. There were 40-50 restaurants within a 5 minute walk of my old aparment. Indian, Thai, Korean, upscale, dive, hipster, normal. Everything, and it was all good. Food here is bland, the options are very limited. Basically fast food + Chinese is "Eating out" is this area. If you're a food snob, have a palate with some sophistication or are used variety, rural America is pretty bleak.
3. People. People are MUCH nicer and polite, but also fairly slow (both in terms of speech patterns and...intelectually). Irony is not something they understand. Everything is taken at face value, religion is of high importance, physical fitness is not emphasiezd. People are very out of shape, in general.
4. Environment. Everything is very spread out. Lots are huge. I see one other house from my living room window. In the city, 50,000 people lived within a half mile of me. Roads are wider. Streets are totally spotless. But everything looks a little beige and drab. There's not much attention to style or design. Everything feels utilitarian, basic, simple, traditional.
All in all, I prefer the city with all of its faults, its crime, filth and loneliness. Life out here is too simple. Boredom is setting in already and I've only been here a few weeks.