Which of napoleons mistakes were the most costly

If you are talking about Napoleon Bonaparte then here:
the first mistake was the Continental System which killed more of his empire. (the Continental system was a blockade that stop the trade between Britain & Europe BTW)
the second mistake was the invasion of Russia. this one is common because the weather was cold and it was hard winter. The french were little uneducated in military.
the third one is the peninsular if i am correct. Napoleon took out the Spanish king and replaced him with his brother. the Spanish got mad and Spanish fought french which lead napoleon to take another look at Spanish. 
hope i helped this is all from my head :D