I agree, it's easier for the pilots, but the ideal time for the flight attendant to make it happen is while one of the pilots is in the bathroom-
AFAIK most flying of commercial planes is actually done via autopilot once you're at cruise, and in that case there would be little immediate risk to say choke the pilot out. While it's more difficult, I certainly see it as being a definite possibility, given that regardless of how thorough a background check may be, the airline can't guarantee one of their employees won't go psycho.