It is very hard to give you clues without knowledge of the domain model and data. It seems you already tried a lot of stuff. My advise is to pinpoint the locations where the app is slow. In a datagrid for instance you could not show the total count for instance because that already could slow the datagrid when there are a lot of records. Also check the search fields and especially the search fields that contain references.
In your logs you will see the retrieves that take a lot of time. Try to analyse why these retrieves take so much time. Analyse the XPath queries and double check if they can be made simpeler.
And after you pinpointed alld the chokes you always could get paid advise from Mendix Expert services. They have a lot of experience with these kind of problems, but indeed it will cost you but your developers will learn a lot from these people.
Regards,
Ronald