If I delete all residents/townies will it break my game?

No, it won't break anything.

No, it won't break your game. I've done this myself to create a blank template when starting a new game. Just one thing you should know if you have the Get Together EP. That pack requires a minimum of ten clubs in the game at all times. So, if you delete all the premade clubs, the game will create ten clubs and fill them with newly created townies.

Unless someone has created a mod for this, there's no way to stop it from happening. What I did for my 'blank' template was keep at least one Sim in each of the premade clubs. Some Sims were in multiple clubs, so at least I didn't have to keep ten premades. Over time, once you've made ten clubs of your own you can then delete all the premade clubs.

Also, you can't stop the game from generating townies for various positions around the worlds and 'extras' it thinks you need. For instance, if your Sim goes to a park, the game will generate a bunch of Sims. If they go to a gym, the game will generate a trainer, the library will generate a librarian, etc. Just an FYI... :)

EDIT: Okay, I just re-read your post and it sounds like you won't mind if the game generates new townies. You just want fresh faces in your new save. I was thinking you wanted a completely empty game, which isn't possible. Opps! You should be fine. :)

The only thing you need to do is make sure you have 1 household marked as played, so you can't delete every household, you have to have just 1. Having no households marked as played makes the save feature wonky, It will not work properly and can overwrite other files.

Other than that, you can delete all the households, just make sure you evict them from any lots first. Deleting households who are assigned to lots can cause the lots to loose all the furnishings.

Thanks, guys! I just created my new save and killed everyone in the world, LOL (except my one sim, of course).

One thing you'll want to do is to evict out the household before deleting them. Otherwise, it will make the houses empty when you attempt to move in a new family.

No breaking. The game will recreate any sim that is strictly needed. I think NPCs are picked from a pool, so there will be a certain chance of getting a few of them that you have met before.