This is a difficult question to answer because A) it would have been different for different types of people and B) because it is a matter of opinion as to which thing was the most difficult.
If we are talking about things that would have happened everyday, you could argue that the hardest thing was having too little to eat. According to the link below, for example, poor people might have nothing more to eat than a couple pounds of bread each day. That's a lot of bread, but it's not much variety.
If you were a woman, you might say that the hardest thing was doing without all of the conveniences we have today. Having to cook all your meals over a fire would be a real pain. So would having to cook fresh every day because there were no refrigerators.
If you look at things that weren't going on every day, a really hard thing would have been the lack of medical knowledge. Imagine having to worry about a cut getting infected and killing you. Or having to worry about dying giving birth.
So there are lots of things to choose from as difficult things about life in this time.
Everyday life for the peasants of the Renaissance period was, in the words of Hobbes, "nasty, brutish and short." Peasants lived in one room huts, often with chickens, pigs, etc. Pigs were allowed to range freely, and the family normally owned only one cow, which was used for milk, butter, etc. Diet normally consisted of porridge, basically grains boiled in water with salt, some course bread, and beer as the basic beverage. They ate vegetables in season, and the only meat was pork, which was often tough and lean. Because of hard work, most people were bent over, had fetid breath, and were infested with intestinal worms. Everyone slept in a common bed, and privacy was unheard of.
The nobility lived a different lifestyle, but hardly better. They were quite class conscious, and refused to eat vegetables, as this was the fare of "poor folk." A typical meal lasted for hours, and consisted of large amounts of venison, duck, and other game animals, consumed with large amounts of wine. It was not unusual for a nobleman to literally pass out under the table. As desirable as this seems, the diet of the poor was probably better. They received some protein from the germ of the grains, vegetables they consumed, and a sufficient amount of fiber. With little or no fiber or vegetable matter in their diet, the nobility often became bloated and had intestinal problems. Consumption of large amounts of meat often led to gout, an extremely painful ailment. Sometimes the gout was so severe, that they could not walk, and had to be carried in sedan chairs. Barring childhood illnesses, etc., the poor often had a longer life expectancy than the nobility.