This is what I did and it appears to have worked.
Took an existing user with @olddomain.com and configured an Outlook profile and ActiveSync.
Changed the primary SMTP address to @newdomain.com and kicked off a DirSync. I left the UPN @olddomain.com and left the @olddomain.com email address as secondary.
After the Dirsync ran, both Outlook and ActiveSync picked up the sending address of @newdomain and neither prompted me to login again (since the UPN didn't change).
I removed the @olddomain.com ActiveSync connection and set it up again using @olddomain.com and it still connected and worked. There is no need to update the user's email address on ActiveSync.
I removed the @olddomain.com Outlook profile and set it up again using @olddomain.com and it still connected andn worked.
It appears that changing the primary SMTP doesn't impact profiles if you don't change the UPN and keep the old primary SMTP address as a secondary.