Considering that 100% of the population use a computer, and many have more than one Internet connection, I would say that empirical data speaks against that. Mail just works for almost everyone. While it is true that you have to enter more settings in your mail software than should be strictly necessary, because of things like SMTP filtering, that is a solved problem.
As long as your protocol survives being NAT'd you're probably fine on today's networks. Because I hope you are not considering the use case that people start putting up Tent servers inside their office networks.
In fact, overloading port 80 will cause more problems than it will solve for home users. They will not find it at all straightforward to run both a web server and a Tent server from the home connection, for example.