There is a ton of activity in the space, of course. I would first glance at the ECMAScript efforts of late (ES6 and ES7 in particular). You'll probably need to use Node.js, since it tends to be the center point of JS development, regardless of the tools and frameworks you choose.
The first piece is your build tool. Grunt and Gulp are the two top build tools. Gulp is more recent and seems to have more uptake. If you haven't written a build script (e.g., gulpfile.js) I recommend building one up from scratch rather than using someone else's. You could use others' for examples of what to do, but build your own from scratch according to your needs, as you go. You'll learn more and understand the whole thing that way.
The next choice is whether to use a transpiler or not. The two biggies are Babel (ES6 transpilation to ES5 or ES3) and TypeScript. You can skip this step at first, but it will be a foundational aspect to your build, so don't wait too long. If you do skip it, loop back once you've made your other choices.
The final big choice is framework. The big ones right now are React and Angular 2. There are many others, of course (Vue, Inferno, ...). You might try a few efforts here to learn about them if you don't have a clear initial default choice.
There are secondary choices depending on which main framework you choose. For example, if you use React, you will likely need a client-side store. Flux used to be the default. Now it's likely to be Redux or, more recently, MobX.
There hasn't been a better time to be a JS dev. There's still a lot of churn, but there's also more stability than there has been in the past few years. You can stick with technology choices for a year or two without major disruption if you make course corrections. Good luck!