Most milked franchises 

[Soundwave]

Mario spin-offs sure, but if you're talking the main Mario games, Nintendo is very frugal in how they use Mario.

Super Mario World (1990/91)

Super Mario 64 (1996) - Five Year Break

Super Mario Sunshine (2002) - Six Year Break

Super Mario Galaxy (2007) - Five Year Break

That's a looooooooooooong time between games. NSMB Wii is coming 3 1/2 years after the NSMB on the DS, too.

Super Mario Galaxy 2 is really the first time they've come out with a Mario sequel within 3 years.