Calvin Hendryx-Parker from SixFeetUp gave an interesting talk at the Plone Conference, advising strongly to only use Plone for its strengths, and not try to make it do what it's not optimized to do.
Plone does a tremendous number of things extremely well, but not everything. So at what point does it make sense to integrate a 3rd party application? Reinout van Rees blogged about the presentation. The bottom line: "Our time is valuable. Why waste it by trying to hammer a square peg in a round hole? Pick the right tools for the right job and let Plone do the things it is good at."