The Sicily Channel in the Med. I've bagged the Aquitania twice - over 45k tons and only two eels (guess I didn't do the job right the first time. They managed to refloat her from over 1000m!)
There are plenty of large ships in the Med and the Sicily Channel is ideal for ambushing them. If it's under 5k tons, I usually let them go as there will be another one in a couple of days.
If you want advice on large ships in harbour, check out:
http://www.subsim.com/radioroom/showthread.php?t=130620