Nemesis Mode's description states that it makes bosses notably harder, but I could barely tell the difference and I still beat the first three bosses before they could even finish their attack pattern.
I recommend adding a bunch of random prefixes. Every boss is guaranteed to have at least one, and sometimes multiple on very rare occasions. Here are a few ideas:
- Electric: all the bosses projectiles move faster and shock you for small amounts of damage just by being near you.
- Fire: projectiles move faster and ignite you on contact.
- Ice: projectiles move slower and slow you down on impact.
- Poison: projectiles move slower and leave trails of damaging poison gas.
- Explosive: projectiles are converted into mines that activate when close enough to you and explode after a short delay.
- Homing: projectiles gain sensitive homing properties. The boss and its projectiles change color depending on what prefixes it has.
Continued suggestions in the comments: