How many Domain Admins (not Local admin) are best practice for an org of 5000 users 20 Dcs and 4 sites? Does MS have a matrix fo this?

I think that you should have at least 2 domain admins and delegate administration to other users . I don't think there is a matrix for that. This posting is provided "AS IS" with no warranties or guarantees , and confers no rights.

Per Site? Per FSMO site?

I think that it will be better that the domain admins (2 at least) will be in your FSMO site. You can delegate Active Directory Site Topology Administration . I think that it will be better to delegate the Active Directory site toplogy administration to two persons in each sites. You can also delegate administrative tasks on OUs. I always recommand to have at least two persons with the same role because if one of them is absent, you will find the second to administer the environement. This posting is provided "AS IS" with no warranties or guarantees , and confers no rights.

what about in the event of one or two of the FSMO role servers going down and the two admins are not around?

The effects depend of the FSMO role that is down: PDC Emulator is down: Accounts lockcout can not be forced, users will be unable to change passwords, domain computers will be unable to sync time .... RID Master: Administrator will be unable to create new Active Directory objects ... Infrastructure Master: In your case, I think that you are using a single domain so there will be not effect if this role is down Domain naming Master: Unable to create new domains Schema Master: unable to change Active Directory schema This posting is provided "AS IS" with no warranties or guarantees , and confers no rights.