You see the question of "best debut album" kicked around a lot, but I can't recall hearing it asked for film. Thought of it while watching Get Carter yesterday and being impressed to find that it was Mike Hodges' first movie considering how assured it is in its choices (although he had done television work before*, and I'm sure a lot of first-time feature directors are also coming from short films or assistant director/writing/acting roles on other movies, so maybe this is a somewhat stupid topic).
Anyway, Citizen Kane is the overwhelmingly obvious choice. Reservoir Dogs would be a lot of people's pick, I'm sure (though not me). Breathless, 400 Blows and Hiroshima Mon Amour are some obvious ones (I've never seen the third, and think the first two are not the best by those directors.) Being John Malkovich is up there. I'll go to bat for Lock, Stock and Two Smoking Barrels (appropriate since watching Get Carter made clear how much Ritchie ripped off from it). I think a lot of comedies could qualify (Spinal Tap, Airplane...)
I think my pick would be Repo Man. What else is up there?
*Specifically a children's thing called The Tyrant King, which Wikipedia has informed me has "The Thoughts of Everlist Davjack" by The Nice as its theme song - apparently Floyd, the Moodies and Cream were also on the soundtrack, which is pretty hip for 1968.