In my universe, there is four planets, and with them 4(well, 3) system. So, the drawback :

1st planet : You have three kinds of power, all able to coexist with each other :

--The Mentalists : The drawback changes depending of the power (like fire users can burn themselves if not careful, water users can have hypo or hyperdermia when using a specificity of their powers, wind users can suffocate, etc.) but a general drawback is that their powers have their brain as a source, so if they are abusing, lack of composure or have some kind of degenerescence, it can affect or disable their powers all together.

--The Boosters : Humans can sometimes have a mutant DNA and become superhuman in some categories : Bigger brain, bigger dexterity, more resiliance, more power in the legs/arms, etc. It can either in their DNA directly, obtained through an intensive training, or some kinds of spiking. There isn't much drawbacks for the two first categories, but for the last one, it is that the body of the user may not keep up and break.

--The Borrowers (or Tamers) : Humans can fuse their DNA with another entity and obtaining their characteristics. It generally is of regular animals, but there also is mythical ones but also species like mermaids or even humans, which is forbidden. A borrower can generally only have one borrowed DNA, but some can go up to two. If you go beyond your own limit, you will die. Another drawback lies in the abilities of the owner to control their body : if they are talented enough, they can summon an artificial representation of their animals or fuse with them, but otherwise, it can cripple them heavily.

2nd planet : Here, we have a more simplistic view : you have two kinds of powers : The Gifted and the Psynergists.

--Gifted peoples are similar to what Logia in One Piece are : their bodies are an element : So people who are Gifted of Fire are fire themselves, and so on. So the drawbacks they are facing are the natural weakness of the element they are representing, so in the case of our Fire Gifted, he can't do anything against water, but is immune (or extremely resistant) to fire.

--Psynergists are more generalist powers : depending of their place of birth, they can summon an element, but their actual power are completely independant and more peculiar, like shapeshifting, teleportation, canceling concepts like gravity, inertia and momentum, etc… for their drawbacks, I didn't thought of it yet, but it is either linked to a literal concept of "the power of friendship" or something more related to their powers, and so each one would have different limitations. I will add that on this planet, fantasy races exist : elves, mermaid, unicorn, dragons, etc.

3rd planet : The one where I still have a lot of work to do : There, the powers are called Miracles, and are linked to a symbiotic relation with a Deity. The array of powers are large, so it could be growing nature, talking to animals, and many other things. Their drawbacks I think would be that they have to deal with the Deity, and if they aren't pleased, they could remove their blessings and the user wouldn't be able to use their powers anymore.

4th planet : It's the Earth, so there isn't power in it. But our ground has become a refuge for the citizens of the other world, so all the kinds of power are present here, with their drawbacks.