Generally, the major flight finder sites are reliable. There is no real issue there.
Having said that, they do not guarantee you the best price on any given flight on any given day. I usually book direct with the airlines but when looking for a flight recently I found a tour operator who had a cheaper price ($299 vs. $419) for the same flight on the same day on the same airline. The point being there is no best answer.
You should also consider that if any LCCs (low cost carriers) service the route you want to fly, that most of them are not on any flight finder sites because they do not pay any commission to middle men. So the sites like expedia, opodo, etc. do not list them.
It does sound from your comment in #4 however that what you are looking for is more of a package holiday type thing. It might help if you say what you are specifically looking for. For example, if you wanted a flight from Canada to the UK the best prices will be from Canadian Affair or Air Transat (the $299 vs. $419 example I mentioned above) and you will not find them on any flight finder sites such as expedia.