i had sand in a 55G and for the most part i loved it... only had a few problems though.
1) sand ALWAYS ended up in my filter, clogged it and nearly burnt out one motor
2) yes the fish waste will settle on top of the sand, but in my experience it was heavier than the sand so almost impossible to vac (even using a full water changer connected to a sink).
3) i could barely get my plants to grow in sand... i even upgraded my lighting to something better suited for plants and still had issues. also, i was always re-burying plants due to shifts in sand, it never stayed in one place like gravel does.
don't get me wrong though, i loved the sand aside from the above mentioned issues. so if you have already thought of solutions to these then you're quite a few steps ahead of where i was... sadly these issues may steer me away from ever attemping a sand substrate tank again