Gardening is invaluable to me - my Sims always have some produce in their inventory for a mid-day snack. It's really useful when you want a kid to get his homework done and don't want to spend an hour feeding him a 'quick meal' (which then ruins his dinner). Parenting is also huge, since I always play families and high skills open up all sorts of interactions with the kids. And I love painting, because the paintings are so pretty, and handiness, because my Sims can improve their stuff.
Least favourite is mischief, for the reason people have cited above - it's just mean. Herbalism would be better if it weren't so impossible to collect the bugs. (That's one thing that was better in Sims 3 - bug collecting didn't require as much hand-eye coordination, and it was easier to find them.) I like the ability to teleport and my Sims basically live on the superfood salad, so wellness is a must, but it would be even better if the interactions it opens up had an effect on other Sims. (That is, if you have a Sim with high wellness skill, they should be able to help another Sim to relax by talking about detoxifying or whatever.)
