This is a difficult question... and, like most infrastructure questions, relies on how your organization is setup.
We're a very large public school district, so our audiences are quite complex. Here are some examples and experiences we've had.
Building-based (all users @ school a, all users @ school b)
Department-based (administrative departments such as MIS, Curriculum, Finance)
Subject-based (all math teachers, all science teachers, all reading teachers)
Grade-based (all 7th grade, all elementary, all middle, all 12th grade)
Thankfully, we had existing Exchange group setup for this same hierarchy, so the transition was simple and natural...
For a corporate environment, it could be something like.
All Portal Users
All Executives
All Office Staff
All Department A
All Department B
All Sub-Department A
All Project A
All Project B
etc.. or
All Portal Users
All London Office
London/Accounting
London/HR
London/Marketing
All Brisbane Office
All Singapore Office
All Dublin Office
All Madrid Office
Thankfully, the choices are pretty limitless and can be designed to match whatever organizational structure you need. Most anything you can delimit in Active Directory, you can assign a "member of" audience to it in Audiences.
Our structure, at least, is still a bit too complex for audiences we wish to specifically target. For example, to specifically target 7th grade reading teachers _is_ possible, but requires an extra overhead to find those specific individuals and place them into an AD Global group. We, at this time, do not have groups that contain these individuals. At that point as we're still migrating into the product... baby steps!
Hope some of these ramblings help a little bit.
Regards,
David
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David R. Longnecker
Web Developer
CCNA, MCSA, Network+, A+
Management Information Services
Wichita Public Schools, USD 259