I wish GitHub had a "This bug affects me" or +1 button so the comment history stays clean of "me too" responses.
This has been a huge frustration for me when it comes to bug tracking. I have multiple clients who just aren't technical people and when they see the wall of options that bugzilla and mantis offer it causes them to give up and email me directly. I even tried vbulletin for awhile, but that had its own problems.
GitHub (once you get past the signup) is perfect in this regard. Just open a ticket and then comment on it.
I wish GitHub had more in regards to bug tracking, for example being able to create states (open, in progress, closed) as well as labels.
These days I'm sure there are comparable solutions but having the issue system through github means one less service I need to track, which is also nice (client gets code, client has issue tracking, done).
With all that said I wouldn't use github issue tracking for complex multi-stage applications where the environment is an important factor in the problem.
I was using Pivotal Tracker a few years ago for a large-ish project, and really wanted the client to use it.
It didn't strike me as terribly hard for reasonably bright people, but I under-estimated habit and the degree of resentment some members on the client team had about their pet project being changed.
Assorted attempts at education (I made a really nice screencast!) failed; I was still getting e-mail with Excel or Word docs attached.
We finally came to an understanding and started using Google Docs.
BTW, Github issues is not so bad. A key feature for me for any bug tracker is a Web API, something I can talk to using a command-line tool.
I wrote such a thing for Pivotal Tracker (my Pivotal Slacker Ruby script, now abandoned) and later hacked up a program called GHissues to pull items from Github.
I've been in the position to choose bug trackers for two companies I've worked for, and I still don't feel competent to vote.
It just seems funny to me that a company that also makes a bug tracking system has a really bad one coupled with it's version control hosting. It makes some sense, but it bugs me.