Well, that really depends on what you're into. There's a lot to do and see in Osaka and the Kansai area. You can find some good info here:
http://www.japan-guide.com/e/e2157.html
Just a few things...
If possible you should spend one night in a Ryokan (tradional japanese hotel) with an Onsen (hot spring). If you have company I would choose one with your private hot spring bath connected to your room
If you're into baseball you should try to get tickets for a Hanshin Tigers game. I'm not really into baseball but I really enjoy the atmosphere in the stadium as they have amazing fans.
I would also visit Kyoto (I spend a few months there every year)... takes less than an hour by train to go there. Kobe and Nara are very nice cities as well and not far away either.
Have a good trip