I've spent a great deal of time researching this very subject.
I've found that Austin, TX, the major cities in Tennessee, Raleigh, NC, Atlanta, GA, Downtown Philadelphia, PA, and Pittsburgh, PA are the best.....for me, anyway....
I'd rank them:
1. Pittsburgh
2. Austin
3. Philly
4. Raleigh
5. Atlanta
My love for Pittsburgh stems from it's cheap cost of living, proximity to where I grew up, it's awesome, down to Earth people (the best people in the US, honest), and it's natural beauty. Driving out of the Fort Pitt Tunnel and seeing the city literally appear from nothing is breathtaking. There is also very little traffic for a major city. I can get from one side of town to the other in an hour any time of any day.but usually much less time than that. The only negative is the winters...but I can deal.
I like Austin because it has nice Winters, low cost of living (the Pflugerville area is hella cheap if you can handle the suburban sprawl...), and self described "weird." The chicks at UT are freakin' amazing, too. They also have fast food Mexican restaurants that taste better than the sit down Mexican restaurants North of the Mason-Dixon line.
I like Philly because, like Pittsburgh, the people are cool. The winters suck balls though. Cost of Living is kinda high, but you can get a sweet loft overlooking the Delaware River for $500k that's right next door to Dave & Busters...
Raleigh is a REALLY up and coming town with a damn young populace. They have more singles than anywhere that isn't a college town. It's cheap, weather is perfect, and many of my classmates wound up there. I fear that it will become a mecca of pretentious dinguses at some point soon, though...let's hope not...
Atlanta is a cool town, too. I love their public transportation system...it's really efficient. It's cheap to live there, the weather is awesome, and it's the capital of the New South....
But that's just me....