Inside the Manor, there are countless artifacts to find such as the Colonel Pete cartoons and Constance Hatchaway's hatchet. The cartoons are in front of the stairs in the foyer, while the hatchet is in the Library rafters. The manor features several unique enemies, and Mickey encounters the Mad Doctor here.
If you finish all of Madame Leona's quests, no matter how long you took, you won't have to deal with the Slobber that appears. Talk to her instantly after you settle the ghosts however and you'll have a fight on your hands.
An easily missed gremlin lies in the Foyer. The painting of the Chernabog can be thinned if you ride the tables up to it. Settle the poltergeists with Screeching Sam's quest before though, and you can't get to him at all.
There is yet another gremlin in a secret alcove in the Stretching Room. He is the hardest to find if you don't know where to look that is.
Originally, the manor's graveyard was set to appear, but was scrapped due to scheduling reasons.
Lonesome Manor can be seen if you look through the windows of the first level in Epic Mickey: Power of Illusion. It seems to use the concept art from the first game when looking at it.