Oh man! THere’s like an infinite supply of activities. Check out Metromix. There’s a ton of stuff on this site. Restaurants, concerts, clubs with live music, museums, tours, Navy Pier, world class shopping, etc. etc. etc. Metromix.com
There are some museums near the waterfront. The Museum of Science and Industry has long been a favorite of mine. The MSI’s building is a piece of history, being the only remnant of the 1893 World’s Fair still in its original location.
Up Lake Shore Drive from the MSI is The Field Museum of Natural History, another World’s Fair remnant. From 1893 to 1920 it was in the building now occupied by the MSI.
Where will you be staying? Downtown? Gold Coast? Near North Side etc.?
It’s a great town. Much larger than you realize. The museam campus is a lot of fun but do yourself a favor and get out of the loop. If you can, get up to the northside and hang around the lakefront. A lot of bars, restaurants and cookie shops in and around that area.
I wouldn’t do Navy Pier unless you’re into carnival rides and shopping malls, because that’s mostly what it is. Fun for a family outing, but it isn’t the best Chicago has to offer. That said, if you’re interested in a boat tour of the Lakefront, Navy Pier is the place to pick one up. There are several choices.
I haven’t been to either the Sears Tower or the John Hancock Center’s observation deck, but I’ve heard that the Hancock one is better, even if it isn’t quite as tall. They’re both near the Loop, but the Hancock is closer to the lakefront, on North Michigan Ave., which also has nice shopping and restaurant options.
If you’re into history, the Chicago Historical Society usually has something interesting going on. They even have the bed that Abraham Lincoln died in, including a blood-soaked pillow!
The observation decks are very weather dependent. if there’s cloud cover, don’t waste your time.
A weekend is just enough to get a taste of what you want to do next time you’re around.
People watching/shopping, N. Michigan Avenue is great. The downtown area (Loop) has some shopping also, and some bargain places. It’s a different crowd there, but it’s worth seeing.
Second the museums, all of the ones in the museum campus around the lake and Roosevelt are worthwhile. If you can get south, by the U of C, the Museum of Science and Industry is still a blast. That whole area is a day if you want it to be - it’s the neighborhood where the Columbian Exposition was held, and there’s still a lot of fine architecture there. I’d be careful you go exploring there with someone that knows their way around though (except I’m not available, sorry) because a couple wrong turns and you’re in neighborhoods you probably don’t want to be in alone if you’re not from there.
Navy Pier isn’t JUST malls and carnivals, as Kalhoun pointed out. The dinner cruises are a good time. The food is very “eh”, but if it’s pleasant out at all, you can’t beat the view. or, if you want to stay on dry land and eat, there are some good restaurants right on the pier.
If you’re into ethnic foods, there are a ton of great restaurants in the city. I’d say this though - rather than finding a (for example) mexican place downtown or on the Gold Coast, find a neghborhood place away from downtown. City Guides can usually steer you in the right directions with this, so it’s not as hit or miss as it sounds.
I’ve been to both the Hancock and the Sears, and the former is MUCH better. Unless things have changed, they have a restaurant/bar on the top floor, or second-to-top. It’s quite expensive, as you’d expect of a restaurant with a view, but what the hey, you’re not going to be around there every day.
I heard recently that The Berghof German restaurant is going to close, if indeed they haven’t already. Definitely check that out if you’re into that type of food, for you won’t get another chance.
The Navy Pier has a museum of stained glass, if you’re into that. And the International Museum of Surgical Science, if you’re into THAT, is on Lake Shore Drive in the Gold Coast area.