The biggest thing is that there is simply less to do. I remember that meetup.com and similar sites had maybe a dozen things listed within 50 miles and they were generally things like "Senior Citizen's nature walk" and "Small Business owner social group". Finding a D&D group? Much more difficult and you'd better be prepared to drive long distances? Makerspace/hackerspace? non-existent. Your favorite musician is generally going to stop in the big cities and you're going to have to drive to get there.
If you're a foodie then your choices are going to be restricted to fast-food, a few traditional local places and maybe one or two Chinese restaurants. Food trends might reach you a year or two after your friends in the city. And hopefully the only Pho place within an hour drive will be decent. Museums will be small and limited and sporting events will be limited to the local recreational/high school teams.
Buying things will be more difficult. Your amazon packages will take longer to there. Socially, you're much more limited. The dating scene is much more difficult (which goes 10x if you're not straight). And the existing social groups can be insular and difficult to break into.
That's not to say that it's all bad. Such places can be incredible if you tend to be more introverted and love the outdoors.
Overall it strikes me as an "the green is always greener" situation. I think that, at best, most people will try it out for a year or two and realize that they miss trivia night at the bar/concerts/sporting events/parties and move back.