alien invasion for a good cause
What if aliens got tired of waiting for us to get over our differences here on Earth, and realizing too many people still had an "us vs. them" mentality, decided to start a war against humanity just to force us to finally unite, to fight the aliens.
invisible guy becomes feminist
Some guy becomes invisible, starts doing all the things you'd expect someone to do in an "invisible man" story. The twist comes when he starts witnessing street harassment of women, because the men harassing them have no idea there's another man around. Because he's invisible. Maybe he becomes an invisible crusader against harassment, or something.
mad scientist saves the world
Hero who normally fights a mad scientist must enlist the scientist's help to save the world from invading aliens or monsters or something.
musical
This guy lives in a musical, but one day he finds himself unable to just sing and dance automatically. So he goes to a doctor and discovers he has some disease that affects the part of the brain that allows people to spontaneously burst into fully formed song and dance routines without practice.
superhero conflict
There's a secretive, seclusive group that live on like an island or something, who raise superheroes (with naturally occurring super powers) to eventually go out into the world and, you know, do superhero stuff. But there are also normal people (without powers) who are born and raised in mainstream society, who decide to become superheroes. And while on the surface the two kinds of heroes are on the same side, beneath the surface there's a usually unspoken distrust that many heroes of each type feel toward the other. The story would focus on two superhero partners, one of each type, who are good friends, and dislike the fact that so many heroes distrust each other (sometimes to the point of barely concealed xenophobia). And as tensions rise, potentially leading to a war between the two types of heroes, these partners are caught in the middle, with conflicted loyalties, so their friendship (and partnership) will be tested as never before. (Also, maybe there's a faction that's trying to give people powers artificially.)
alternative technologies
In the future, Earth is at war with an alien race. Both races have roughly equal levels of technology. However, the actual methods of achieving the same things are different (like how the Federation uses warp drives and Romulans use quantum singularity reactors). And both sides can learn to use either their own form of technology or that of the enemy to their advantage, in different ways, often by thinking outside the box. For example, both sides have transporters, but one race beams a person's deconstructed atoms through space and reassembles them at the destination, while the other race makes an exact copy at the destination and destroys the original. The latter race might realize they can use this technology to create unlimited clones...
See more story ideas on my message board. Also see TV show ideas.