After upgrading from Portal for ArcGIS 10.5.1 to 10.6.1 on Windows Server 2012 R2, we noticed significant performance delays when using Portal. Loads were taking almost 5x the expected time.
This is a high-availability "single machine" deployment, and only Portal was experiencing issues, meaning accessing the server admin site was a breeze with no problems.
Re-indexing, installation repairs, dropping to a single machine, and adding resources did not help. There are no apparent log issues.