There are two ideas that I have thought of recently.
ONe would be a game where Bunsen invents an alternate demension, and as soon as he unleases it, a creature form that demension kidnaps Beaker, and as a cool twist, players cna choose to play as either Bunsen, who must rescue Beaker, or play as Beaker, who escapes. When playing as Beaker, it's like playing the game backwards. Beaker would have to defeat a main boss at the beginning of the first level (maybe it could be easier for Beaker to beat him than for Bunsen to). So there are two patterns, in opposite order. I don't think any game like this has ever been done. And I would want it to be a scroll screen game, so when Beaker plays, the game would actually scroll to the right, instead of the left. Perhaps many of the levels can have main bosses halfway through the levels, or multiple main bosses throughout eahc level (or appearing at random times, so they can battle the hero at the same point in the game without it being odd that the boss is at the beginning). When playing as Beaker, one big difference is that the character who kidnapped Beaker would return at the end of his last level, which would be the beginning of Bunsen's first level, but Bunsen wouldn't fight him at the beginning.
A Muppet Labs game for the DS would also be good, with many mini-games where the players could test inventions on Beaker.
Another idea would include Gonzo's species (maybe not his family, but the same alien species) attempting to take over the world by turning all earthlings into being just like their species. Howeve,r this wouldn't effect Gonzo, since he is part of that species, and the others apear to be so weird that Gonzo appears normal, and decides to save the world and bring his friends back to normal.