Offense
Easiest - RB/WR, depending on the system/role. If the RB doesn't do a lot of blitz pickup, it's easy....just do what you do. Most don't have a clue how/who to block. WR can be super easy for a lot of spread offenses with limited route trees, but more difficult for teams with checks, option routes, motion, etc.
Hardest - QB. OL is definitely hard as well, but for most it's strength or technique. For QB, it's physical and mental (progressions, checks, reading defenses, blocking alignments, etc) but also the leadership/"it" factor as well.
Defense
Easiest - DEnd/Rush LB. See ball, get ball.
Hardest - S/MLB, whichever is responsible for aligning the defense and making the calls/checks. If you made me pick today, i would probably say safety. They are so important in today's RPO spread offenses and can blow a coverage very easily.