Originally Posted by Polaris OBark

I have two wheel sets on my main (non-touring) ride, one 700c and one is 650b. The primary advantage of the smaller wheels is that I can fit a larger tire. Ideally, the outside diameter of the 650b wheel with a fat tire should be approximately the same as your 700c with a road tire, which would allow it to handle and fit similarly. (Mine doesn't quite do that, due to frame limitations.)

I just put on some 55mm 700c tires on my touring bike, and the handling is rather awkward, and toe overlap is now an issue. In retrospect, I should have had 650b for that width.

The only significant disadvantage I can think of is that 650b road tires might be harder to find in some regions. On my bike that has a set of 650b tires, the frame isn't able to accommodate as wide a tire as I like. (On my touring frame, this is not an issue). Because the tires aren't as fat as I would like, their outside diameter is a bit smaller, and I have some issues with pedal strikes off road.