Option #3 is the best one for sure. You can avoid Detroit AND Chicago, which will be the biggest slow spots on your trip. And you get to avoid the Detroit-Windsor area, the most heavily-trafficked border crossing between the US and Canada. Went through Port Huron/Sarnia once; it was a cinch. And of course, you know you'll be on 465 around the north and west sides of Indianapolis as part of the route XD
If you are traveling on a weekend, the traffic in Detroit and Indy won't be too bad; it's mostly rush hour problems, and there are a few choke points.
The smoothest route and the straightest shot is #3 below - Port Huron-Flint-Lansing-Ft Wayne-Indy-St. Louis.
If you are adventurous or if you really want to avoid truck traffic, you could take US 24 from Toledo all the way to Lafayette IN, then cut down to I 74, over then south on I57, then west on I-70.
Or from Lafayette, take Indiana 63 south to Terre Haute (it's also empty, like US 24), then I-70 (which is pretty busy) to St. Louis. Either of those routes will add about 45 minutes to the trip, though.
Interstates 70 and 75 are pretty heavily travelled with trucks, so avoid those if you'd like a calmer drive.
