I don't think GitHub and Q2A should be compared. In GitHub, the username is itself part of the project. You can have exactly the same project name for different users so you need the user in the URL. In GitHub you do care about who's fork you're browsing. In a Q&A site you don't care that much about whose question you are browsing.
If Q2A used the same URL structure as GitHub, then question URLs would look like this yoursite.com/<user-id>/<question-id> . It is a bit awkward, IMO. I'd compare Q2A to other Q&A sites, such as SO
This question seems to have turned into a "Next release feature requests" :) In order to keep things organized I'd rather not discuss those points but just the user URL stuff. Otherwise, this results in those never-ending discussions that lead nowhere and which I usually try to stay out
I agree with you on having the link to the user profile by ID. Which is a step backwards in what ProThoughts requests in the question, as user ids are just numbers so the URL would look like yoursite.com/12345. However, you can actually apply the same URL change that happens with questions and append the username to the URL (question URLs append the title of the question) so that they look like this yoursite.com/12345/John+Doe (being "John Doe" the user handle). This is what StackOverflow does and I like the idea. That way users keep the same ID even if they change their username (BTW, with the number is enough to find the user, the username is just there to beautify things a little bit)