Basically the reporter said, are you more worried if you lose one engine of two versus one engine of four on the 747/707/etc. To which the pilot replied, losing an engine is always a serious problem. Maybe if we ever get to my copilot saying we've lost engine 43 will it be a non issue.
More engines just means more chances for failure. All I know is losing any engine isn't something you treat lightly.
A military pilot called for a priority landing because his single-engine jet fighter was running "a bit peaked." Air Traffic Control told the fighter pilot that he was number two, behind a B-52 that had one engine shut down. "Ah," the fighter pilot remarked, "The dreaded seven-engine approach."
In small multi-engine planes where single-engine flight is marginal, the safety advantage is terribly clear. You have a better chance if an engine fails, but you also have a lot more failures.
It's less of a problem in large airliners, where the margins are higher and the training more thorough. The safety advantage is clear enough that all large airliners have at least two engines. Still, there are accidents that stem from a single failed engine on a multi-engine airliner:
http://en.wikipedia.org/wiki/Kegworth_air_disaster
http://en.wikipedia.org/wiki/American_Airlines_Flight_191
http://www.delawareonline.com/article/20060614/NEWS/60614001...
That last one is not technically an airliner, but it's the same basic category, and I think it's a particularly interesting example as they had four engines, but managed to screw things up badly enough after losing just one to crash anyway.