In life time sim type game. (One in which you play through a life time of character or other arbitrary period of time) How much should early choices good and bad affect things later on?

If you use drugs heavily at the start to boost your rep with a gang and make tasks easier should that lead to health problems and complications later in life?

Should getting involved with the wrong people have risk of blackmail should become successful and honest later on?

Should an ex-girlfriend come back into your life with an illegitimate child asking for support, and for you to do the right thing.

Like wise should an old friend from the street now turned successfully politician provide you the odd favour when they can for all you did for them back in the day?

Being healthy and active mean when you're young mean you are less likely to suffer illness as you age and are eligible for the latest biotech advances.

Well, if you ask my opinion i`ll say this kind of consequence system would be the perfect A-life game. But let`s face it,with the current AI technologies it isn`t possible in that way.(sure you can write a huge decision tree for every single character in the game, sure you can make your system as multi-agent as possible, but again the choices have limited results.)
what i`m saying is,with an average budget for your project, the results wouldn`t be fantastic.

One of the things that make games 'fun' over Real Life (tm) is that you can fix mistakes or travel back in time and redo bad decisions.

In my experience, mistakes made early on that have long-term negative consequences that cannot be fixed in some way really spoil my gaming experience.

E.g. that supposed trash you found at level 1 and discarded is a critical key that you need to open the door to the last boss mob.

E.g. as you're learning the game you choose some skill specialization and it ultimately is completely gimp. The game has no mechanism to correct that.

You could make the game so you can still play no matter what you became. It's like if you became a junkie, all right, you have junkie challenges, you haven't "lost" because of that.

I think it's important to figure out where you want to come down on the gameplay / sim debate. If it's more important to send a message about choices and even fairness in life and you want that life portion to strongly resonate, I'd make the consequences long term (possibly even random).

If you want to make sure its still a game, though, I'd vote in favor of a fair start with the player being responsible for all failures.