the anime, manga, and game are three different worlds:
1) Miduho doesn't exist in the anime or manga
2) in the anime, Keitaro, Naru, and Mutsumi never go to Okinawa a second time
3) Moe-chan doesn't exist in the manga
4) Kaolla's siblings don't visit during the manga (which was pretty much the only section of development that would have worked in the manga as well)
5) (this should be the most obvious) Shinobu starts living at Hinata house BEFORE Keitaro in the manga, and AFTER in the anime
6) Nyamo isn't an orphan in the manga, and Pararakelse is QUITE inhabited
7) Keitaro doesn't seem to have his pot fascination (i.e. digging up pots during plot points...) in the anime
8)