Well what type of games do you enjoy playing?
Action, Adventure is mine so that's usually what I stick to.
What I like to do is start with everyday situations.

For instance traveling home you get stopped by bandits.-

That's cliche and done but what if a portal opens and monsters flood through it, killing all the bandits and wounding you.

When you wake up, you drag yourself to town and pass out.

Upon being nursed back to health you find that you have a strange mark on your body, that seems to glow. The town is suddenly attacked by the same monsters and your mark begins to react....

I could go on but my point is, by starting with something simple, you can go into a random place.. as long as you come back later and explain WHY.

For instance.. it turns out that the mark on your body is related to the phenomenon of the monster portals, and through the course of your adventures, which seem to be random and quirky(or serious and death defying) you uncover the threat of a greater evil. The evil doesn't have to be threatening the whole land. Maybe just a town or city, maybe even threatening to devour your soul. Unless you find and defeat it..

My point is a million things could happen from the beginning to the end. What you choose to make occur will directly affect how your game will turn out.

Does your character need to gather items to defend himself or empower himself? (farming or gathering)
Does the mark give him powers as he grows (unlock skills)
Does he need to travel far to reach his goals and if so how will he traverse vast distances?(warps portals?

Also how do you keep gameplay engaging? It gets old whacking stuff repeatedly. But if the "whacking" has a goal, then the player has a reason to whack. For instance, maybe giving the character different types of strikes.. Fast and Hard. Hard strikes have a chance to knock back monsters and crush defenses whilst fast strikes have a chance to stun.

The mark could give supernatural powers(shoot beams, fire the lazerrrrr)

I don't want to make this too long but a good starting place to help a game unfold is picking a situation you would find difficulty in and adding something unique or out of place to it.

... I would never have thought of such a brilliant plot :o ! You're writing the book, and I want to read it! >_<

@Raimo I guess what you could do is... read a few books based upon your liking? Try to fuse them together and start changing things from there.

Just like what Dariuc was saying (At least what I think he was saying), Something so Simple can become something so complex.

I guess, if you want to think Biology/Science... You can think "The Cell". It's so small(Simple), yet it can do so much as to... Pump Oxygen into our Blood Cells(Complex).