I'm going to agree with the last poster (and disagree with most of the others) and encourage you to travel by car. With 2 weeks in the U.S., you'd go crazy without the freedom of your own car.

If it were me, I'd choose to fly into DTW - a nice airport, relatively few international flights, so customs should be less of a hassle, and probably cheaper rental cars than the other airports.

From there, you could drive to Chicago in half a day. You'd be looking at a long day driving to get to the east from Chicago. Once there, the large cities of the east coast are spaced relatively close together - Philly to NYC will be a few hours, NYC to Boston, half a day or so. Philly to Duke would be a haul, but again, a one day trip.

I'd pass on Orlando, unless your college-aged nephew really HAS to see Disneyworld. Instead, make your Boston-Detroit loop pass through Cornell, RPI, U of Rochester, etc., then head to Niagara Falls and drive through Canada to get back to Michigan.