Lots of spoilers! Perhaps an answer or two also.

Rating: Null/10 (9 June 2003)

Lord knows I'm not the sharpest tool in the shed and I sometimes don't think before I say or do something stupid but I too have an angle on this film It may be way off, but then, so is this picture.
Some thoughts and lots of spoilers: Have you noticed that when we go to sleep we sometimes carry some of the residue of the day into our dreams with us? Just bits and pieces, usually. A little bit of everyday `reality' swept in that gets skewed and twisted in the fugue of sleep. Add to that a healthy dose of despair, and guilt and you could be on one hell of a trip. That, I think, is what we have here in the film Mulholland Drive. We start with the perspective of one climbing into bed and falling into a pillow here the dream, and the skewed reality begins. Diane, now Betty, hits L.A. straight off the jitterbug circuit where she's just won a dance contest which has prompted her to try her hand at acting (makes since, right? Jitterbug contest winner = great actress pre-req). Sounds like something straight out of a silly old fifties movie right? Coincidentally, as you find out later in the film, Diane in an extra on the set of a movie set in the fifties.

In Diane's dream, Betty hasn't got a care in the world. Everyone is so nice to her and her situation couldn't be more perfect; Her aunt is conveniently away and has left Betty her fantastic apartment. The aunt has also got Hollywood connections and has arranged for Betty to go in for an audition, her first ever, and of course, they love her (with all her jitterbug experience how could she fail?). She's just perfect for the part. She's not had to suffer the pain of rejection. Rejection and failure, those elements seem to me major players in this picture and missing thus far in the film. It seems it's at this point that reality first tries to creep into her dream. The pain of not getting a part in reality is glossed over in the dream by some strange characters making the director cast some unwanted for the part. We are also now taken on some side venues that, to me, are just remnants of the real world that Diane has drug into her dream but are, in the end, inconsequential. Now comes the unavoidable part Rita (Camilla in the real world), Diane's love interest. There's no way around casting her in the dream. She's been Diane's focus for far too long for that. In this role, Rita is the beautiful, sole survivor of a horrible car accident who conveniently has amnesia so she can be anyone Betty's mind needs her to be, except for the person she really is, of course. Here, Rita is dependent on Betty, she needs Betty. Just the way Diane would love to have been needed by Rita.
In the real world Diane is all messed up. She wants to live the Hollywood dream but, the reality is that she's not a star and probably never will be. She's infatuated with a woman, Camilla, who is a star but is no longer interested in Diane. Her obsession's new romance with the director of the film that both women are working on is rubbed in Diane's face and she snaps. Have you ever noticed how that when something bad is going to happen, something you were dreading but powerless to stop, it seems to occur with agonizing slowness when it does finally happen? The point where the director announces the impending nuptials between himself and Diane's intended, plays just like the eponymous scenario. During this scene we see the cowboy walk by who will be pulled into the dreams later simply because of his presence during this powerful turn/crack in Diane's mind. Diane goes off the deep end and hires someone to kill Camilla. The agony of loosing Camilla and the guilt of having her killed is too much for Diane. She sleeps all day, trying to escape the reality. For the brief time we do see her in the real world is when she is awakened by her neighbor, collecting some things left behind after the two swapped apartments. Diane is in her robe, hair a mess looking like she's been in bed for days. (Anyone who has been or knows someone that's been depressed, knows this is probably the case). The neighbor informs Diane that some detectives came looking for her again. Undoubtedly investigating Rita's disappearance/death. One of the last times we see Diane, is her standing in her kitchen thinking back on the things that led to this point. To the point where guilt and despair cause her to take her own life. The next time we see her in reality is when the demons have come home and she has to shut them out for good
As far as the homeless guy in the back of Winkie's goes (note the name denotes sleep: catch a few winks  Winkie's, Ok maybe not) to me he could represent the dirty little secret in the back of Diane's mind. She did, after all, hire someone to kill Rita. The blue box might represent Diane's life; she has the key but never opens it herself. Once it is opened by Rita, we see that it is empty. Rita is the one that holds it in her hands and opens it up. In the end though, it's dropped by Rita and we see them no more.
As far as the old couple that could be the finger of accusation. The innocent and honest seem to magnify guilt and shame just by their very existence.
To me the strangest thing in this movie is the aunt walking into the room after Rita drops the box as though she heard it drop. Did she feel a disturbance in the force? Did she somehow feel Diane's life pass. We don't even know if she really is Diane's aunt or just another inane character having been dragged into Diane's dream.
Whatever the case, this movie will keep you guessing and asking questions long after it's viewed. In my opinion this is one of Lynch's best. One director that understands that film is a medium in the world of art.