We did it, twice.
We lived 5 minutes from my wife's parents, three siblings and three grandparents (2 paternal, 1 maternal) for almost 10 years. We were two hours from my parents. Both did a lot for us, helping remodel and work on one house, and then a full on basement remodel in another. I, however, didn't have any "great" friends there.
I had an opportunity to move about 30 min from my parents and two hours from my wife's family. Had some really good friends there from the three years we were in the area. My stepdad was always around to help me with things, we could drop the kids off at my folks' house and go away for the weekend, great school for the kids, etc.
Then came this opening, better job with more open ended opportunity, better stability, more $$ which would allow my wife to stay home full time, etc. The kicker? 10 hours from my folks and 12 hours from my wife's family. That and it's flipping cold up here. The job is good, though not without stress. But, we've carved out a good niche already, have some awesome friends and all in all, it was definitely the right move. It helped that both times, all family was supportive and knew it was a good opportunity.
It's tough, but in my situation there was a feeling that it was the right move, and I knew that deep down. Sounds corny, but I also had other chances to move that I didn't take because they didn't feel right.