Freeport hasn't gone entirely systemless as Green Ronin also released a True20 rules version.
Systemless books are weak in that they don't provide the crunch that supports the fluff. For example, taint and honor rules that support the notion of a society where corruption and honor are important factors. Just saying "honor is important in society X" isn't as strong as introducing rules where players receive direct benefit (or penalized) by playing honorable.
Another problem I see with systemless books is understanding the power scale for foes. How do I know which monsters are stronger in this setting and how do I translate this into meaningful stats? I need a measure of degrees to create appropriate encounters for my players.
I think both True20 and D&D 3.5 have done great in this regards. As long as I have the core books, its very easy for me to pick up any new setting book and run with it. In my current desert adventure, its the core + Sandstorm. Systemless books are interesting for ideas, but I don't think I'd every pay the same price as buying a setting book for the rules I'm running.