Ode to tags
Let's say pygtk doesn't compile for you on osx due to an obscure automake error. Would you send it to the python mailing list? or perhaps to the gtk mailing list? etc. No, you ask it on Stack Overflow and give it all the relevant tags!
But hey, does it belong on Stack Overflow, or on Server Fault. It's related to programming but you are installing pygtk because you are the sys-admin, so maybe it should be on Server Fault, but on the other hand, one might face this problem when trying to install it for his personal reasons, so maybe it can belong on Super User?
It seems like the split to several "topic sites" goes against the philosophy of tags. Perhaps there's a better solution than splitting to different sites, one that is consistent with the tags philosophy. Maybe like:
Instead of splitting to different "topic sites" (SO/SF/SU/MSO), create "master tags" (programming, sysadmin, power-user, meta-stackoverflow). Each question must have at least one master tag. Users can not create "master tags", they are "fixed", or decided by the site admins, to maintain order.
If someone is only interesting in viewing power-user questions, he'll view the questions belonging to the "power-user" master tag (currently he goes to superuser.com).
In the case of the example question (the "python gtk osx automake" question), it may belong to all three master tags mentioned (or maybe there would be parent master-tags, like "computing").
This may also give more freedom to the site's admins to easily extend the scope of the SO family websites. Perhaps they would want to also allow science questions, or even heated political debates, in this awesome platform. In this way it won't require separate domains and accounts, and would allow the users one convenient gateway to the "internet questions world".
Comparison to current solution and backwards compatability
The way I see it, this solution can be implemented in a totally backward compatible way. Everything in SO gets assigned the "programming" master tag, etc. The topic sites can resume to exist as a site where the default shows question of their respective master tags.
When asking a question, it can get a default master-tag from the domain you used to access the site. Tag auto-completion is only offered for tags that "belong" to this master tag (A tag can belong to several master tags. It belongs to it if any question was asked with this tag in that master-tag)
So I don't see how this will cause clutter as Jeff suggests. In fact, if you limit a question to have only one master tag then imho this is (almost) exactly equivalent to the current "topic sites" solution.
The only difference is that karma will be shared. But if this is seen as a bad thing then this can be solved too, with master-tag specific karma. This idea can be extended to tag specific karma as well.