I think most of the people complaining about the save system either haven't played, or are missing the point of the design. Yes. Design.
The 72 hour mode has so much going on that in the first playthrough you will not, ever, not ever get it all done or be successful. You will fail. But you will level. Frank gets stronger, faster, can carry more weapons, powerups, and learns new moves over time.
If you fail a mission, yes, you can reload and try again, but it's best to hit "Continue" instead of "reload". The main plot may stop, but the time keeps ticking, people still need saving, psychopaths still keep showing up, and the helicopter will still come for you at the right time. It's a sandbox. Not a box.
As of your next playthrough (six hours for a full games worth - PACKED with stuff to do and ways to level), you will be stronger, faster, and more knowledgable. You will accomplish more, get further in the story (and likely unlock it all) and continue to enjoy the game.
If you save crawl your way through the game, the way PC games have taught us to, you will not have this "rebirth" experience, and you will not experience the way the game was designed.
You must unlearn what you have learned.