A boat tour is a must do! The Chicago Architecture Foundation has fantastic, knowledgeable docents, though I think there are lots of great options at this point.
Agree with going to Wrigley if you can - it's a special place.
A drink at the top of the John Hancock (Signature Lounge) is a great way to see the city from up high without too much time, money or effort.
Here's another fun place for a drink with a view: http://www.cindysrooftop.com/ It's not at the top of a skyscraper (just a few floors up) but has great views of the bean/park/lakefront.
I agree with skipping Navy Pier, unless you're intent on going on the ferris wheel or taking a boat trip out onto the lake (both of which are fun, but still)
Renting bikes on the lakefront can be a great way to see the city. This is probably better earlier in the day, since the lakefront path can get busy in the afternoon
We live about an hour away... when we do get downtown and have time, we look for food that we don't have close to home - great authentic Korean, Ethiopian, Indian to name a few. The appeal might depend on what you have available nearby at home though.
Check what festivals are going on the weekend you are in town, then decide if you want to go check it out or avoid the crowd, lol.
-Christine
DD, 9/07
DS, 5/09
and a very tolerant pup