The main difference I can think of is a virus may affect all drives connected to the system. If your external is unplugged, it is a little safer in that aspect alone.
I use internal though because it is generally faster data transfer and easier because I don't have to hunt down or plug in a drive each time. Possibly more spin-ups and spin-downs (which wear the drive) each time computer boots though. I turn on an off my system a few times per day :/ Also, I prefer hard drives with external power since I never have luck with USB-power external hdd's. They always just sit there and click and occasionally don't receive enough power, even when using a 2USB power/ data to mini USB data connection (double amperage), which messes up my...