In the slightly altered words from Animal Farm, Two Wheels Good! Four Wheels Bad!
I think I'd need to see a lot of scientific evidence that says a 4 wheeled bag is ergonomically better to use than a 2 wheeled one - and it will really depend on what sort of journey you do. If you do taxi to the airport and hotel then any is fine. If you're taking public transport, then 2 wheels have more stability. I've seen several tourists struggling to hold onto their 4 wheelers on the tube while the 2 wheeled one. But the space issue wins it for me. Every bit of space is valuable to me when travelling!