Are you already locked into a specific weekend or do you have some flexibility?

If you have flexibility, then I'd build the trip around the Cubs and King Tut.

Other'n that, Field Museum (in general, not just the Tut part), Art Institute, architecture river cruises, a morning run along the lake up through Lincoln Park Zoo (stop and say hi to the seals, please), and just hanging out in Grant Park are my recommendations.

For nightlife, it can go any one of a million directions. Chicago is probably the best eatin' town in the world - just pick your favorite two or three unusual ethnic cuisines and go from there. Hit the basics - deep-dish pizza, a Chicago dog, a great burger, etc. - for lunch, but go for something more eclectic for dinner. Definitely explore some of the neighborhoods outside of the Mag. Mile area.

I'm sure many will disagree with me on this, but I honestly didn't find the Magnificant Mile shopping all that interesting or unusual. Big department stores, a Crate & Barrel, a big bookstore, a bunch of high-end clothing and jewelry retailers, etc. Stuff you can find in any other big city in the world. Not many uniquely Chicago boutiques. If you like shopping, maybe try the Maxwell Street Market (although I haven't personally been to it in many years) on Sunday. There's a little more weirdness there. Plus plenty of streetfood.