Great question, I see as many newer vehicles broken down on the side of the road as I do old ones. The things that have given me issues were always the things that I never suspected. One time had a bearing go on the belt for the air conditioning, another time after driving a nightmare road had a U joint go.
When you are driving if you notice something like poor handling or a strange noise find a garage and have it checked out without trying to push more miles out of it. I hear from so many people that "It had been making a noise for a couple days" as they are stuck on the side of the road with a bad transmission.