Hard question to answer because a lot of the perks are so different that what one person might find easy another person might not.
Sharpshooter requires precision and good specimen prioritization. There's a very very high skill ceiling for this. On the other hand, someone who has good aim might not know a lot of other things that would make them a good player, like where to stand to be the safest, which kite routes are good for sharpshooter, etc. There's really a lot more to think about than aim-->click - this goes for any perk actually.
Demo and Firebug are similar in that not knowing how to play the perk at an adequate level makes it extremely easy to be a hindrance to your team. Is it hard to play either? Not particularly. But there is a threshold of knowledge needed in order to make the perks effective and then becoming 'good' at the perk would be maximizing the effectiveness. It doesn't take much to realize this when you all of a sudden play with a good demolitionist, and fleshpoudns - even multiple - barely live past 2 seconds as soon as they're spotted and the team always seems to be safe because of great crowd control.
Commando needs to be quick on their feet and the trigger - there is tons of trash to clear in this game and with the AR's you're the best bet for killing it. Specimen priority becomes HUGE for this perk, and it changes based on what kind of teammates are standing behind you along what kind of specimens are in front of you. Too many times I see a siren, a husk, 4 crawlers, a few stalkers and both a sharpshooter and commando are focusing down the siren and husk - only to soon be overrun by the stalkers and crawlers. Or a fleshpound comes out with a siren escort and the commando suddenly develops a frozen trigger finger.
Beserker often gets pinned as 'the hardest perk to play' but I disagree. It is just different. It involves learning a dodge & weave style of play because you're using melee weapons instead of shooting. The run speed makes kiting an attractive choice but imo, zerk also allows for the sloppiest playing because of damage resistance along with the speed. It means the difference between a good beserker and a bad beserker can be huge - but they might both be able to beat a difficult wave negating the relevance of any skill difference. Regardless, it does take some getting used to and there is a certain level of adequacy required to play the perk well that might not be immediately obvious to people first playing this perk (which I think contributes to the 'zerk is hard' thing).
Medic is pretty debatable. What does being an extremely good medic mean? Keeping the team healed? tanking when necessary? Also killing trash? being able to solo each specimen if required? Medic seems like after you take the 'keeping the team healed' part out of the equation, being skilled at every other perk will help you the most at being a good medic. For example, a Medic who is a very good sharpshooter as well will probably be better off carrying an m14 or Lever action while a Medic who is also a very good Demolitionist might benefit the team more by carrying an m32 grenade launcher. Both would be great medics, but have completely different styles and set of skills
Support - it's pretty obvious that this perk has the lowest 'be effective' threshhold but again, there is a world of difference between a support that knows when, what, and how to shoot things and one that just mouse1 shotguns everything on sight. Being able to pull off combos and techniques consistently takes practice. The differences between a mediocre support and a great support I think are very subtle but make a big impact. For example, a great support will have made EVERY shot an effective one, and if in a situation where he is one of a few alive and clutching out a wave, won't have to worry about ammo as much as a mediocre support. Little things like this DO add up and can be the difference between a wipe and surviving in a lot of cases.
That's really what makes any one good at any perk, it's mastery of the little nuances that pop up and can be situational along with survival fundamentals like basic perk skills, map knowledge, specimen priority, and good decision making. Just imagine all the times you've been killed by that one crawler that surprised you from behind or were one shot short of getting that fleshpound/scrake. Maybe had you avoided some husk shots or any earlier little bit of damage you would have had enough armor left to save you. That's what I mean by the little things, and how they can be very subtle, and can apply to every perk differently. This is how a sharpshooter who has mediocre aim can seem better than the sharpshooter who has laser-shots but keeps getting ganked by crawlers by standing infront or under spawns or infront of every ones LoS.
Things like accuracy have an almost infinite skill ceiling and benefit every perk but I would say it benefits sharpshooter the most. There are too many other things involved along with that and the other perks to say Sharpshooter takes 'the most skill to be good at', but I think that will be the answer most people will give you.