If you can take advantage of the non-major border crossings, do that. I don't know what's near Niagara Falls beyond that big bridge. (Been there, done that, a few times, in a car.)

People ride between Quebec and Vermont (and New York) all the time. It's not an issue. I keep trying to get my wife to do a ride with me to Montreal, but she doesn't think she can handle it.

Edit: What Martianone said.