Especially if you're a windows user the first thing I do is change the default trackpad settings
-disable natural scrolling (why switch your brain back and forth between two methods)
-enable tap to click (will make your trackpad last longer)
-enable two finger tap = right click (again tapping as opposed to clicking will prolong the life of your trackpad)
The trackpad is one of the best things about Apple computers so figure out what works for you and enjoy
Also figure out where you want the dock to be. IMHO having the dock at the bottom is very wasteful of space. I prefer it on the side and actually now I autohide the dock so all of my screen can be for apps.
Calibrate your screen. After calibration the screen almost always looks better than it did out of the box (at least in my experience).
Learn keyboard shortcuts (especially for spotlight) so you can be super efficient!
You'll have to google this but unhide the library folder. It will make your life easier later. Unlike windows on mac os you can find almost anything associated with a program by simply looking through finder (and knowing where to look). For example I needed to know where my kindle books were stored so I could convert them to another format to read on my tablet. Without access to the library that is impossible. Other examples: printer drivers, the custom calibration profile for your screen, email etc. All found in the user's library folder that apple hides by default.
I'm of the opinion that most of Apple's default settings are dumb but their computers are brilliant. You just have to tweak them a bit.