What are the drawbacks for manufacturing a large airliner capable of water landing?
Maintenance. Ditching survivability calls for overwing engines, as underwing ones act as scoops and torque the aircraft. But underwing engines are quieter for the pax and much easier to access. Plus, you'll need to make most of the openings airtight, and regularly inspect and replace the seals.

But of course weight, drag and extra fuel are a big deal - with better materials you'll still be picking between better reducing fuel usage or improving ditching survivability. The latter is also only helpful in controlled ditchings, which are mostly being prevented through engine reliability.

That said, airliner design has shifted from "don't crash" to considering crashworthiness at every stage. So it's possible that ditch-worthiness might become a larger factor in design. But it's going to take a couple high-profile high-fatality controlled ditchings for the authorities to make the call to sacrifice fuel efficiency for it, which is currently a big deal due to rising oil costs and AGW concerns.