Having the engines half way out along the wings make it fairly inefficient if one fails. Having them close to the centreline of the aeroplane, such as a DC-9, VC10, BAC 1-11 & 727, means it has a lot less of an effect should you lose an engine. In a 4 jet in the configuration of the A340, 747 and 707 type, lose two on one side, and compared to say the VC10/IL62, life could be very interesting, and lead to a very aching leg!
This fact has yet to stop any 4 engine plane, let alone a twin engine plane. On September 11th when all flight got ground a watched a C-5B land with #1 & #2 motors flamed out, only had the right side, and it made a perfect landing like all were still working, they just landed long since only the reverser's on the one side worked.
That was landing, which is quite a different kettle of fish to take off. Having chatted to some USN 707-frame drivers last year in the desert, their biggest fear was losing two on take-off. Not guaranteed to ruin your day, but certainly going to make it more difficult.
As for the initial part of your reply, I guarantee that at some point, it has.
Here you go, when GE was testing the GE-90 for 777, they mounted it on the 747, and since it was so powerful they cut the regular 747's motors and just flew it around on one motor. They show it around the 2:40 mark.
http://www.youtube.com/watch?v=tT5EZ5itYH4When I was in technical school, we were told that Boeing flew the 777 on a test flight on one motor just to show that it could operate safely on one motor for extended periods of time. But I can't find that Information.