Just sharing ideas for each of the themes, using a top down shooter as the starting point.

1. Limited memory Play as a computer, load power-ups into memory, unload previous power-ups to use better ones.

2. Ridiculously overpowered Ammo replenishes faster the longer you play, with the weight slowing your movement, power-ups could be empty magazines for you to fill up.

3. Your life is currency Health doesn't regenerate, but HP can be collected from enemies, which could be swapped for other power-ups.

4. Side effects Shooting enemies make them move faster, missed shots spawn extra enemies, power-ups hurt you when collected.

5. Space exploration Power-ups are invisible, and can only be found by exploring the room.

6. Change the genre of a classic video game Agar.io as a top down shooter?

7. Only one enemy Enemies are actually parts of the final boss, the more of them you destroy, the smaller the boss will be when you reach it.

8. Risky powerups Power-ups are like a coin flip, and can sometimes hurt you instead of giving you a power-up.

9. Shelter You're in a house, and you need to keep shooting HP at the walls to stop them being destroyed by enemies.

10. Color changes everything Your weapon is a paintbrush, and you paint enemies different colors, such as red to slow them down, green to poison them, or blue to freeze them.

11. Everything has a price Pay to get more HP, pay to kill enemies, pay to pause the game, you get the idea...

12. Contagious Shoot enemies with viruses, which slowly kill them, while also making them more dangerous in the meantime

13. Tiny town Top down shooter in a tiny town?

14. Mutation Your bullets randomly change enemies into either power-ups, or bigger enemies.

15. No upgrades, only downgrades Start the game with all the power-ups, after each wave, you need to pick which one to give up.

16. Underground The enemies are underground, and you're on the surface?