A few major reasons:

1. They had no oil. They were due to run out in 1942 so attempted to take the Soviet oil fields. This famously failed, and then it was basically the beginning of the end.
2. They didn't finish off the RAF when they had it on its knees. This meant they couldn't take Britain.
3. They underestimated the USA massively

Basically Germany was at a huge disadvantage from day 1 and the route to victory was very narrow.