Note on Glitched 100 Gold Medal Achievement (it's fixed): From the developer regarding a patch fixing gold medals - "The bug that was fixed was one where if the player launched Defense Grid 2, but did not play any levels before quitting, the game would cause certain stats to be reset, including how many gold medals you had earned. The time when you last launched the game and didnt play a level would impact how many gold medals you must get to get master strategist. Going forward, your medal count will not be reset if you enter the game but do not play a level."
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For the most part this game is fairly self-explanatory. It's a tower defense game. Enemies spawn, go to your core housing, and then try to flee the map. You stop them using towers. If you mess up, you can press 
to go back in time and try to fix it. There are a few game mechanics I do want to take note of here but most of the game can be learned simply by following my guide in the Story section of the walkthrough.
Towers
There are 10 different towers.
Boost - These are blocks you place on a slot that the enemies can't pass through. They allow you to build another tower on top of them and they also give the towers you build on top of them a little bit of extra height (towers can't shoot through eachother always - the line of sight in this game is a bit weird). They also allow you to build upgrades to the towers. You can choose from Overcharge (damage boost), Disruptor (reveals stealth and disables shields) and Score Boost (boosts score and isn't necessary unless you want to place on the leaderboards).
Gun - This is your bread and butter tower. It has a medium range and is very good at taking down shields and medium-sized enemies.
Cannon - This is a longer range Gun that does more damage. The trade off is that it fires slower. You build these in key places where they will be able to hit enemies in a wide range. They're also quite good at taking down bosses.
Missile - An even longer range Cannon essentially. Very expensive but quite effective at single target damage.
Temporal - This tower slows the enemies and is extremely good. It can't be Overcharged. Upgrading it only increases the range.
Laser - The laser fires quickly and puts a damage over time effect that hurts enemies even after they are out of range. A Laser is very, very good at taking down fast enemies. It's always a nice tower to have if you can place it somewhere it will be able to hit enemies multiple times (and by that I mean the enemy's path will take them by the Laser multiple times).
Tesla - A lightning tower that is good at taking down shields and does some area damage. I don't personally find it that useful and use Disruptors and Cannons to remove shields instead, but it can have its uses.
Inferno - Does area damage in a small cone and can't damage enemies that are directly in front of it. To be honest, I find this tower to be quite bad and completely inferior to the Concussion tower.
Concussion - This is the best tower in the game. Extremely high area damage for a reasonable cost. You'll nearly always want at least one or two of these.
Meteor - The AOE version of the missile.
Tower Augmentations
These are new to Defense Grid 2. At the end of a level you will occasionally unlock a random tower augmentation. You can equip them when selecting a new tower. They make your towers better and you should always have one equipped if you have one.
Score
The way scoring works is a bit different than the first Defense Grid. In the first one, your score was based on how many resources you had at the end and the value of your towers. It's similar here, but not exactly.
Now you get points every time you kill an enemy. You start with a base score for each kill and this base score is increased based on a number of factors. This includes the amount of resources you currently have, how many cores are remaining in the core housing, and how many cores are taken but haven't left the map (either the enemies are carrying them or they are going back to the base).
3. Story walkthrough1. Walkthrough overview
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