You're lucky...I wish I could visit Blacksburg this weekend. For that matter, I wish I could move back there altogether!
Blacksburg's downtown is along Main Street, or Business 460. I'd consider downtown to begin around Miller St. in the south, and end at Prices Fork Rd. in the north. Quite a few new businesses have opened in the last few years, so downtown may have expanded a few blocks in either direction. All in all, the main business district is about a mile long. The heart of town is probably the intersection of Main St. and College Ave. Of course, most of the businesses are geared towards college students, so downtown will be a little quieter than it would be during the school year, but it definitely won't be deserted. Actually, I always enjoyed Blacksburg more in the summer because it was easier to find a parking space downtown!
As far as must-sees are concerned, it depends on your personality. Some of my favorites include Gillie's (mostly vegetarian food, although they also serve seafood), Boudreaux's (I hope I spelled that right...it's a Cajun restaurant), and the Lyric Theater (they show mostly indie films). Of course, there are also plenty of bars, but each one is a little different. If you do nothing else, at least drive or walk around the Virginia Tech campus. Try to park downtown and walk down College Ave. for a couple of blocks until it makes a 90 degree turn to the left. Continue walking straight past the library and you'll reach the Drillfield on the center of campus.
I'm sure new outdoor outfitters have opened since I was in Blacksburg, but I can definitely remember one place. I think it's called Back Country Ski and Sports. It's on Business 460 just south of Blacksburg, in front of the hospital.
I hope you enjoy your trip!