I would start with mocha, but only because I did myself and never regretted it. I still use Mocha with chai.expect(). For front end I use Karma in addition, but that came after a while.
I assume you know about TDD? If not, do it in this direction (IMO):
- Read about TDD
- Use Mocha and Chai Expect as long as you can without any more fuss
- When the time comes when you are used to Mocha and Chai Expect, you're REALLY tired of reloading three browsers manually every time you need to check if you fixed something, and you don't see another way out of it except automating stuff, read up on Karma. Configuring it is a bitch, and you'll run into sooo many edge cases. If you use ES6 and Babel in addition... Well, good luck, buddy! :)
HOWEVER: Once you've configured Karma for a project and it works, your workflow will go faster.