Cross-Dressing Voices: Patrick and Mermaid Man are voiced by Ikuko Tani (an old lady) in Japanese; Plankton, however, is voiced by Chie Matsuraa, a young woman who doesn't even try to match Plankton's English voice.
In the episode "Mid-Life Crustacean", a driver that mocks Spongebob and company shares the exact same voice actress (and voice) as Kevin from Ed, Edd n Eddy. There's even a Shout Out in his dialog...
Driver: Hey, you guys must be lost; Doofus Drive is around the corner!
The Other Darrin: Man Ray's first appearance in "Mermaid Man and Barnacle Boy V" was voiced by Guy Siner and John Rhys-Davies. Man Ray's subsequent appearances have been voiced by Bob Joles.
Every Background fishes voices changed a lot.
What Could Have Been: Apparently Adult Swim asked if the creator would be willing to make a Darker and Edgier SpongeBob show on their network, where Patrick and SpongeBob would be a gay couple, ala Ren and Stimpy. He declined.
Early production sketches indicate the cast was originally human.
Word Of God: Stephen Hillenburg has made it perfectly clear that Spongebob is (despite what most Moral Guardians and the LGBT community seem to think) asexual. He also adds that Spongebob has a chaste crush on Sandy.