Anything mechanical can break and cause issues.
I just sold my 06 2500HD. 220,000 miles. My nephew bought it. If you've seen pics I've posted, that truck got thrashed. It had its few issues, but nothing big. But, 10mpg. I'd hop in it and run to Cali with it.
@Steve is chasing a valvetrain noise in his fresh 300 right now.
The new stuff, well, it's got issues no matter what brand. You do however have that warranty thing to pay for it.
The small turbo engines get decent economy, GM has oil leaks on them. Not sure about others. Last I heard the local Hyundai dealer had 37 cars waiting for engines that grenades. Ford boys tell me the Bronco engines are having issues. I personally don't think small and turbo is the best route even though my wife runs one.
In my opinion, best engine that could be had in the last 20 years, the GM 6.0 gasser. Get it with no variable valve timing, no active fuel management and put gas, oil and coolant in it for however many miles the chassis can take.
In short, cars suck.