The basis of any given tower defence game is the narrow premise of placing towers to defend against some encroaching... thing. Honestly, the rest is quite vague. I've seen some that are meant to emulate doodles on a desk, and the invaders are office supplies. I've seen another where all of the turrets you use are Tetris pieces. And another where everything is made up of weird techno-lasers. These kinds of games are simple, often lacking any real narrative. In their day, they weren't too far flung from interactive click-bait.
Defense Grid came to define itself more by what it wasn't than by what it was. Where most tower defence games were cheap cash-ins, Defense Grid felt like a full game. In place of a nebulous pseudo-narrative, there was an actual plot. The love and care was evident and helped distinguish it from a genre infamous for mediocrity. Defense Grid 2 doesn't have quite the same baggage. The tower defence craze hasn't just subsided; it's been almost completely absent for years. In that sense, Defense Grid 2 feels paradoxically foreign and familiar. All of the elements with which you're likely familiar are there - towers, waves of different enemies, and some McGuffin you're tasked with protecting - but they seem out of place now. The fact that essentially nothing has changed in minute-to-minute play doesn't help.
You'll have a few main different kinds of towers - each with different specialisations and effects. Inferno Towers, for example, are great against groups of weak enemies, while cannons help with fewer, more heavily armoured foes. Which tower is most effective is determined by a combination of core stats - fire-rate, range, and total damage dealt per shot. Earlier in the game you can get by with just a few of each type for generalised coverage, but as the difficulty ramps up, you'll need to consider your choices a bit more carefully. You can upgrade and sell your towers as well, in case you need a bit more oomph or you found you've made a mistake in placement. Overall, though, the basics are straightforward. In fact, with the exception of the narrative, the only substantive difference is multiplayer modes. Now when you've finished the admittedly short campaign (I finished in less than six hours), instead of just trying it again on harder difficulties, you can put your skills to the test against or with other players.