I have a Trek WSD 5200 from a few years ago. It has a carbon frame with ultegra components. My inseam is 28" and ended up with the 47 and it fits well. All the bike shop guys recommended the 50, but it always felt too big. The 650 wheels should not be an issue. They will have more rolling resistance, but less wind drag. Many tri bikes have 650 wheels and triathletes like to go fast.