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.
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.