EXistenZ - The final question "Are we still in the game?" really summarized the first watch experience. You have no clue what's going on anymore by that point.
Same goes for Total Recall by the way - that movie also has you guessing what's real and what isn't throughout 90% of the runtime.
I can't remember when, but I know I saw EXistenZ on HBO somewhere. I first saw it from the middle of the movie and thought "If I watch this from the beginning I might understand it." Turns out watching it again didn't help, but I watched it again anyway. It was sort of like a fascinating disaster.
Kudos to the creators of that film. I don't think I could have come up with that primis.