National Lampoon’s Van Wilder (2002)
Reynolds plays the title character in this modern day Animal House(ish) film about a perennial college student.
Tara Reid (American Pie) also stars in this film.
This film spawned 2 sequels, The Rise of Taj (which does not include the Van Wilder character) and Freshman Year which is a prequel and stars Jonathan Bennet as the Van Wilder character.
Harold and Kumar Go to White Castle (2004)
In this modern day Cheech and Chong style film, Ryan Reynolds plays a small role as a male nurse.
Other stars in this film are John Cho and Kal Penn (as Harold and Kumar, respectively) and Neil Patrick Harris.
This film also spawned a sequel titled Harold and Kumar Escape from Guantanamo Bay, after which Kal Penn quit acting to accept a job in the Barack Obama administration (boo!). However, Penn recently left his job with Obama to star in the third installment, A Very Harold and Kumar Christmas 3D, which is set to be released in 2011.
X-Men Origins: Wolverine (2009)
Probably his greatest role in my opinion (albeit a short role), Reynolds plays Wade Wilson/Deadpool in this flick about the X-Men’s most popular character.
Also starring Hugh Jackman as Wolvernine, Liev Schreiber as Sabretooth, and Danny Huston as Colonel Stryker.
There is supposedly going to be a sequel to this film and there will reportedly also be a Deadpool spin-off in which Reynolds will play the title character again.