Did Mark Ruffalo's character know about Mary and Howard's affair, or not? It's left ambiguous as he implies he only noticed something different about her personality when she was with him. If he's telling the truth, he's just unlucky that his girlfriend can't be with him as she has to work through her own issues. If he's lying and he did figure out what was going on, he's creepy and manipulative.
How are Joel and Clementine going to cope with finding the truth out? The original script had a rather cynical ending where an older Clementine would go back to Lacuna intending to erase him - and being told that they have continued to do it over the years. That seems to suggest the two of them will learn nothing from their destructive relationship. However it's shown that Joel does his best to try and keep his memories from being erased when the procedure's actually happening. So perhaps they will give things another try and work on their relationship. Or simply they could decide that the whole ordeal isn't worth it and stay broken up.
The first time we see Lacuna, it's a shiny doctors' office. Later, we see a run-down van and cobbled-together equipment. The shiny doctors' office is a false memory implanted by Lacuna; it doesn't exist.
Though, strictly speaking, the concept of implanting the memories was never introduced in the movie so we don't know whether it's possible at all in that universe.
Clementine's reasons for breaking up with Joel are how he never opened up to her. In trying to keep the memory of her he puts her in all the dark places he never let her into.
Also, of course Joel wants to keep his memories of Clementine, the procedure erases the most recent memories first. As the movie goes on, Joel probably forgets that he broke up with Clementine at all.
Joel doesn't remember "Oh My Darling Clementine" because, when trying to save her, Clem was in a memory of Joel's mom singing the song. Clem got erased from that memory, which by extension erased the song.
Fridge Horror: When Joel initially meets Clementine, he is well aware of the song frequently associated with her name. As a result of the procedure, he has no memory of it, despite its memory only be associated, not originated, with her. If details as insignificant as songs are being lost because of the mind wipe, what else were people losing? There are also a vast myriad of ways this procedure could be used in incredibly unethical ways - implied by Howard's pressuring Mary into having it done after their affair.
A little one concerning the song: it is stated that Joel's favorite toy during his childhood was a Huckleberry Hound doll. Maybe not horror, but having the memory of your favorite thing as a kid is still sad when you think about it.
When Joel goes to get his memories erased, look at the things the other patients are holding (the relics of people they're trying to forget).
After Joel's memory erasure is completed, Lacuna still have absolutely no idea that he tried to resist the procedure. One wonders how many of their clients realized they didn't want to go through with the procedure halfway through but were, like Joel, unable to stop it. Granted, the Lacuna employees react with surprise when Joel goes "off-map" and tries hiding in older memories, but perhaps it had simply never occurred to any of the other unwilling clients to try that.
From the deleted scenes, Howard pressuring Mary into getting an abortion during their affair explains why his wife's reaction to the resurgence of Mary's affections after the wipe was "Don't be a monster. Tell the girl."
Some of the mental images are disturbing - like the guy who literally has no front in Joel's memories, or the instance where Joel temporarily retreats into an "erased" memory. Not to mention scenes where reality apparently decays around Joel as the memory is erased.
Hell, just the idea that an essential part of your memories can be erased in your sleep. And you get to watch it happen.
Rewatch Bonus: The first portion of the movie makes a lot more sense after watching the movie a first time.
The scene under the covers when Clem talks about her "ugly" doll and Joel begging "let me keep this one."
Clem and Joel's first meeting and Joel's last goodbye to her memory.
Joel changing his mind about having the procedure after reliving a particularly fond memory of Clementine, and helplessly pleading for it to stop.
When Joel wakes up but is unable to talk or move. He is only able to stare at them with a look of sheer desperation in his eyes as they resort to sedating him.
There's also the reaction of Howard's wife discovering him and Mary kissing. All she does is sadly say "don't be a monster. Tell the girl" - and Mary discovers that she was previously in love with Howard and pressured into erasing this.