The Suicide Theory[]
It is shown that whenever Luigi was talking to either Toad or Professor E. Gadd in the Telephone Room, lightning would strike the room, and it would reveal a silhouette of Luigi's body being suspended in mid-air. It is believed that Luigi had actually committed suicide by hanging himself from the ceiling, and that Luigi's Mansion is chronologically the last game in the Mario franchise.
Luigi Commits Suicide in Luigi's Mansion? Theory of the Week
King Boo is the ghost of Bowser[]
Despite the Boos appearing in other Mario titles, King Boo did not debut until Luigi's Mansion and serving as the main antagonist throughout the series. The previous game in the Mario series from Luigi's Mansion was the N64's Paper Mario, which ended with Bowser being defeated and blown up. The post in the Mushroom Kingdom gives the news that Bowser has been defeated and will likely never return. With Luigi's Mansion being the next game to follow, it could be possible that Bowser actually died, and his ghost seeks revenge to capture the Mario Bros and imprison them in paintings just like the portrait ghosts were. Bowser's death is further confirmed by fortune-telling ghost, Madame Clairvoya, who emphasized her shock to foresee Bowser and saying how Mario "soundly defeated him" and questioned if King Boo revived him somehow.
This could explain why King Boo claims to vow revenge on the Mario Bros for defeating him in the past despite this game being his debut appearance and why during his boss battle that he gets a Bowser suit to fight Luigi, reclaiming his old physical body. Bowser already led an army of Boos in the past installments as Mario did have to get though ghost houses that were on Bowser's orders to stop Mario on his quest.
Vincent Van Gore[]
Vincent Van Gore is the last portrait ghost to battle before King Boo. He is a talented artist (parody of real Dutch artist Vincent Van Gogh) who demonstrates his ability to bring his artwork of ghosts to life from his paintings to attack Luigi. Could Vincent be responsible for the ghosts that run amok in the mansion and even be responsible for the existence of the other portrait ghosts?
Evidence[]
Throughout the mansion, we see modeled busts of previously encountered portrait ghosts like Biff Atlas and Lydia. He has 5 paintings of the common ghosts and releases them from the painting in 5 clones to attack Luigi.
Counterarguments[]
We see pictures of portrait ghosts when they were alive, implying the portrait ghosts were actually once real living people (or dog ie Spooky).
The Portrait Ghosts were an actual family/the Mansion was a real home[]
Plenty of the portrait ghosts acts as the residents of the mansion as if it is their home. According to Professor E. Gadd, he has been living in his lab for over 20 years, and the mansion only appeared a few days prior to Luigi receiving the fake letter that he won it and how the Boos invaded his lab and set free all the portrait ghosts. When encountering the portrait ghosts, most of them keep to themselves doing their favorite pastime and the ones that attack only do so in defense or retaliation. Most of the portrait ghosts do not even try to fight Luigi should he fail to catch them in one swoop, but instead continue their activity. The portrait ghosts act as if they always lived here and continuing to live their afterlife as they did when they were alive.
For example, the first portrait ghost, Neville is in the study room reading as it is his favorite hobby. His wife is also a portrait ghost, Lydia, who spends her time gazing at the mirror and getting her hair dressed. They have 3 sons, twins Henry and Orville, and baby Chauncey. Pictures of the portrait ghosts can be seen throughout the mansion of what they looked like when they were alive. In the Study Room, you can even read books that were written by Neville and Lydia about their children. They also have a grandmother that lives in the mansion who also has a journal she wrote. Family relations are presented below:
To be continued
The mansion might have also been a real home that was burnt down as it seems to be most of the ghost's greatest weakness and fear. This would explain E. Gadd's testimony for the mansion only appearing days ago but also the portrait ghosts' familiarity enough to reside in the dwelling as it was where they once lived, along with their living photos.
Professor E. Gadd is the real villain[]
Professor E. Gadd is first introduced to be a new ally to Luigi to help fight the ghosts haunting the mansion and saving Mario. However, when the professor introduces himself to the green plumber brother, he tells him not only about the scam the ghosts pulled on the Mario Bros but that the mansion only appeared a few days ago and that the ghosts were once portraits that were set free by King Boo and his minions. Besides the common ghosts and the Boos' intention to harm Luigi, however, most of the portrait ghosts seem to just be keeping to themselves and doing their favorite hobby. It can easily be demonstrated in the first area as Neville is just reading a book, Lydia is just gazing at the mirror, even Chauncey is napping until you rock his horse.
All the portrait ghosts seem to find the painting to be a cruel prison as they resist your capture of them and the boss battles are likely them attacking in defense with the exception of King Boo and Boolossus who are motivated by revenge. Further evidence is from fortune-teller ghost Madame Clairvoya, as she is the only portrait ghost who is ready to return to her painting after aiding Luigi on his quest as she finds residing in the painting to be peaceful. So, for the rest of the portrait ghost who seem to mean no harm at their initial presence, why does E. Gadd need to have them captured against their will? Couldn't Luigi just ask for the key to the next room without catching them? They could also now be under King Boo's orders to prevent Luigi from progressing throughout the mansion. However, this could really emphasize E. Gadd's cruelty to even get Luigi to capture ghost children and only see these spirits as monsters. 
Even King Boo only showed up to infiltrate the lab and release the portrait ghost to include setting free Boolossus, his Boo brethren made up of 15 Boos to make a Big Boo.