This is a question that plagued me to this day, as I have never been able to give a definite answer.
I can never choose just one film for which I can call "the best of the best".
There's just too many to choose from, so I'll just list a few of my favorites that come to mind off the bat.
Juno - Guilty pleasure of mine as far as movies go, but it has it's charms. Witty humour, likeable characters, heartwarming story.
Snatch - Pure genius in a film, anything Guy Ritchie touches turns into cinema gold, even his weaker films like RockNRolla are still excellent when compared to other films.
Anything made by Pixar - Just not the Incredibles, the characters never had the same likability as all the other Pixar films, and the story seemed pretty hashed together when compared with the likes of Wall-E, Toy Story, Finding Nemo etc.
Inception - One of the first films to finally break the Hollywood trend of just making films to make a quick buck. The story alone, along with the fleshed out ideas behind it shows that this truly is a masterpiece in its own right. I urge everyone to see it, it is as good as everyone is saying. Although I still don't rate Leonardo DiCaprio as an actor, he held up pretty well in this.
Saw - The first one will always be an amazing low budget horror, but as a die hard fan, I'd even go as far to say that all of these are some darn good flicks, except for 5. 5 was terrible.
So yeah, those are my few that come to mind, I just don't think I'll ever be able to pick one solid film to be my all time favourite. It's simply impossible.