In your next game(s), you could set "rules", like...

1. Get Level 3 Farming last.

2. Get Puzzle 7 finished last (no one dies).

3. Starve people and when you've only got two (or however many) people left, heal them and see how far you get.

4. Never pause the game.

5. Never take the game off 2x speed (crazy).

6. Get all of your Science Tech FIRST, or any tech for that matter (not always practical).

7. Always pick the "bad" outcome of events and deal with the aftermath.

8. Never pick mushrooms.

9. Keep a strict "no-incest" policy.

The list is looooooooooooooooong of ways to make this game more challenging (and fun, I think)...

Enjoy!

ps I know you said what to do with the game after it is finished, but thought these might help too...

Sometimes after the puzzles are done, I make everyone a Doctor or see how many sets of twins and trips I can get (usually not many). It's not as easy to find things to do once the population is maxed out and they can pretty much fend for themselves.