Frankfurt is very safe so you don't have to worry. The area around the train station is has a bit of harmless (legal) sex trade going on, but it's not unsafe. You don't give an idea on budget, but there are plenty of nice hotels to choose from (Villa Kennedy is probably the nicest, but consider Hessischer Hof or Jumeirah, but there's also Westin, Marriott, Hilton, etc).

Three days is a bit much, but if you have a car you can do day trips to the wine region, Heidelberg, the Black Forest, Rhine Valley, castle route. Frankfurt has great restaurants, by the way...