Earlier quoted context omitted.
I respectfully disagree regarding Fogbugz vs. GitHub issues. I used FogBugz for about 6 years in a major client project (a successful SaaS product). We used FogCreek's hosted solution and were pretty heavy users: different projects, milestones, feature requests, user communication, etc. However, we were unhappy with FogBugz. The UI always felt clunky and slow to navigate, it felt like we were battling FB rather than…
Just a nit on GH issues: email vs web don't mix. Email formatting isn't rendered properly online (line breaks, "> " quoting) - and you can't edit an issue/comment online if you originally mailed it in (it's type is email, and that's it). Editing online is incredibly slow on small machines (zenmode is much faster, but you can't preview).
Have you used the GitHub mobile apps though? I find it's a decent way to keep tabs on issues, add comments, etc., when one is away from a bigger computer. I see that as a big plus for GH.