Robert_Charlton - 7:15 pm on May 31, 2011 (gmt 0)
There are a bunch of competing considerations here.
One question is whether the Reasonable Surfer model [seobythesea.com...] is at play here, and whether the Reasonable Surfer model affects which link the anchor text flows through.
Beyond that there's a question of Google's measures of user engagement, and how putting the most popular link on a page in an iframe might affect that (currently or in the future).
I don't think an iframe in this case is a good idea.
Google's "Reasonable Surfer" - Bill Slawski popularizes the concept