Paul Graham wrote about how to do great work, and he distilled the recipe below in his recent article "superlinear":

• Choose work you have a natural aptitude for and a deep interest in.
• Develop a habit of building your own projects; it doesn't matter what they are so long as you find them excitingly ambitious.
• Work as hard as you can without burning out, and this will eventually bring you to one of the frontiers of knowledge.
• These look smooth from a distance, but up close they're full of gaps. Notice and explore such gaps, and if you're lucky one will expand into a whole new field.
• Take as much risk as you can afford; if you're not failing occasionally you're probably being too conservative.
• Seek out the best colleagues.
• Develop good taste and learn from the best examples.
• Be honest, especially with yourself.
• Exercise and eat and sleep well and avoid the more dangerous drugs.
• When in doubt, follow your curiosity. It never lies, and it knows more than you do about what's worth paying attention to.