District 9 taught the biggest lesson that as loong as you have a good story, acting and visuals, the fact that it isn't a $500 million 3D epic doesn't mean you won't make money. Too many lower budget efforts end up like schlocky insults such as Resident Evil, Ultraviolet, Underworld, etc. If you have a really good story and it looks like it was made by someone with talent, you'll still have a surprise hit.
Then Avatar. Sure, TF2 made a ton of money and was a huge hit for 2009, but it was a crappy movie that nobody really liked. Conversely, Avatar had a good story, pushed the boundaries of film and was an effort worth remembering, such as (the superior) Dark Knight of last year. Instead of just doing well for an annual gross, it becomes one of the biggest hits of the decade. Possibly the biggest. Quality mattered. It also is going to change the way special effects are used in movies.
The rest aren't lessons learned:
The Hurt Locker was a huge critical darling and will likely clean up at the Oscars, it bombed at the box office.
Star Trek proved nothing but the proven rule that rebooting old franchises equals big money (Batman, James Bond, Sherlock Holmes).
Sherlock Holmes proved itself nothing new as it is no secret that star vehicles do well, considering that makes up most of Hollywood's films.
New Moon did not prove vampire fever is beginning (see Vampire's Assistant bombing as well as Transylmania). It proved that women are a strong box office target, especially tweens, and more than romantic comedies will satisfy them. Twilight is not a hit because it has vampires (very watered down vampires), it is a hit because it is a gothic romance, though badly written, given the same hype and budget as a superhero movie.
The Hangover was a raunchy R-rated comedy that was a hit. Like Wedding Crashers. Like Old School. Like Stripes. Like Caddyshack. Like Animal House. Like...
Inglourious Basterds just proved that you should not doubt Tarantino, as much of Hollywood did after the overly long Grindhouse bombed. But it changed no rules or preconceptions of how to do business.
Zombieland? It proved quirky comedies get quirky audiences who love 'em. That is an old rule and if you think zombies made a difference, wasn't Shaun of the Dead a hit? (it was on DVD at least).