Fake Brit: Most of the voice actors in the English-language release of the games put on fake British accents. Actual British-English test players of the game reportedly hated Lani Minella's mockney accent for Luke so much that the British edition completely redubs Luke's lines with English-born Maria Darling. Christopher Robin Miller, however, put on an accent for the Professor so convincing that many players think he is British.
Fan Nickname: The robot dog in Curious Village has no default name, so many players have dubbed it "Gizmo" since it's entirely built out of "strange gizmos." Future Luke has been dubbed 'Legal!Luke', 'Legal', or 'Tom'. Don Paolo is often referred to as 'DP'.
Internet Backdraft: Generally happens in response to changing characters' names in the localization process. One of the bigger outcries was in Diabolical Box when they changed the perfectly fine name of 'Anthony' to 'Anton'. Lots of fans still refuse to use the latter.
Luke in the UK version, he has a different voice than in the US version.
Flora has a different actress from the games in Eternal Diva.
Don Paulo is voiced by Christopher Robin Miller in the games and then by Jonathan Keeble in The Eternal Diva
Talking to Himself: The English-Language release of the games has Christopher Robin Miller taking on three parts as not only the Professor, but also Detective Chelmey and Don Paolo. Considering that in the first game, "Chelmey" was simply Paolo in disguise, this is somewhat appropriate. The Japanese games had different actors for all three characters. Luke follows the same patch - Lani Minella (in the US versions) voices not only Luke, but also Flora, Katia, Celeste...basically all the women in the original trilogy.
What Could Have Been: The second game was first intended to take place in a tropical island where Layton must use his puzzle skills to survive, then the designers noticed such a situation wouldn't be very gentleman-like. Though he did go to a tropical island in Professor Layton and the Eternal Diva.
According to the artbook, Descole was originally supposed to have a large Plague Doctor esque bird mask. This design was later reused for the Black Raven.