Hi,
How many VIPs on the BIG-IP (IP address:port combos) does a client make requests to, that need to be persisted to the same server?
If I understand your description correctly, you could use cookie insert persistence on the BIG-IP to ensure clients are persisted to the same back-end web server. Regardless of virtual directories on the web servers, BIG-IP will send the request to the same IP:port (node) as previous requests so long as the client presents the BIG-IP persistence cookie in subsequent requests.
Take a look at the config guide for your version on AskF5 for details on cookie persistence:
Click here
If the persistence profiles don't give you the functionality you need, try clarifying what you want to do with a rule.
Aaron