I've been to Chicago probably 100 times to visit family. The Sears/Willis tower is OK, but it's pricey. The John Hancock tower's observation deck gives you a pretty good view of downtown and costs less.
The boat tours are a must. They're fun and a neat perspective on seeing the city. Just make sure you're not floating under the Dave Matthews Band tour bus when you go.
The museums are top-notch, especially the Field Museum where you can see Sue, the most complete T-Rex fossil in the world. Don't forget Shedd Aquarium, which is not far from the Navy Pier/Magnificent Mile area.
The food is excellent all over, but you have to get a true Chicago deep-dish pizza. I'm partial to Giordano's, but tastes vary. You could also do a deep-dish pizza tour. I've never done one, but it seems interesting. Also be sure to get a hot dog from Fat Johnnie's. The Mighty Dog and the Mother-In-Law are crowd favorites.