I work in Big 4 at the moment, in my firm's state and local tax group. The networking opportunities and calibre of clientele are truly unbeatable with a Big 4 firm. Additionally, the Big 4 have the resources to provide you with extensive training and, if you wish, they should also give a chance to take on a rotation elsewhere in the US or, potentially, worldwide.
In addition, working in a Big 4 will most likely provide you with opportunities to use other skill sets if you wish; for example, I have an economics background from college. I'll be leveraging that in about six months once I start picking up some side work with our transfer pricing and valuation practice. That's not to say that I wouldn't have a chance to do transfer pricing with a smaller firm; however, the practice at a smaller firm would *most likely* have a smaller, less diverse clientele and would not have the resources to bring in professionals from other groups to assist and learn.
That being said, the hours are longer than you would experience at a national or a mid-tier firm. You also have a larger managerial group to deal with and you have (potentially) more coworkers willing to play politics with their careers and yours. It's also important to keep in mind that the salary will be slightly above a national firm when you start, but they will probably even out within a few years.