Can an iRule loop through values from a file or website?

Sure just create a data group with the hostnames that need to go to the other pool, let's say call it "bigcustomers".

Then use the matchclass command to look for the HTTP host in the request:

 
 when HTTP_REQUEST { 
  if { [matchclass [HTTP::host] equals $::bigcustomers] } { 
     pool bigcustomers 
    } else { 
     pool allrequests 
    } 
 } 
 

You can use an external data group (also called a class file) if the hostnames need to be updated dynamically, then you can just upload a new class file when that happens. Otherwise a plain data group will work fine.

Denny