Having been out for only 5 months, I must say that I'm honestly very impressed with Sanctum 2 (and a bit addicted to it). It has made some definite improvements from Sanctum.
Story:
Initially I was wondering if they were going to add some kind of storyline to Sanctum 2. That was one of the things I'd say to myself when playing Sanctum; "I wish this had some kind of storyline to it." Sure enough, they added one in the form of short comic's. If you search some maps carefully, you'll find more information in-game that adds to the story. While simple, it adds more depth to the game, making it (for me) more enjoyable.
Characters:
The addition of 3 more characters, Sweet Autumn, Haigen and SiMo (Skye being the original), also adds quite a bit more replay-ability to it. Each character has a locked default that is each of the following weapons from Sanctum; Assault Rifle, REX (Rocket Launcher), Shotgun and Sniper Rifle. A 4th addition, Tsygan, was made with their first major DLC, Road to Elysion and came with her own locked default, the Ballista. Each character has traits that are unique. At first I was worried that it may hamper the game with the characters having their locked Primary Weapon, and with the ability to only carry 2 (you could carry 3 weapons in Sanctum, mine being the REX (favorite weapon), Sniper Rifle and Freeze Gun (favorite secondary)), you only had one slot to choose a secondary. This worry quickly dissipated. I honestly like the idea of each of them having "their favorite weapon".
Weapons:
Not being able to upgrade the weapons at all, like you could in Sanctum, actually helps Sanctum 2 in my opinion. In Sanctum you had to either balance, or if in multiplayer, have one go "all turret" while the other went "all gun". I like that they added numerous secondary weapons, evening bringing the Tesla in from Sanctum. I was a bit sad to see that the Freeze Gun didn't make an appearance, but there are still 2 more major DLC's to come, so who knows. Once you hit a certain level (25 if I recall correctly), you unlock the Assault Rifle, REX, Shotgun and Sniper Rifle for use as a secondary weapon. I am fairly certain that Tsygan's Ballista will also unlock as well. I was already (at the time) at cap when they released Road to Elysion. So it was already available as a secondary for me. Also, just as in Sanctum (with the exception of the Sniper Rifle then), all weapons have a secondary function. They added a secondary to the Sniper Rifle in Sanctum 2, which increased is usefulness even more so.
General:
There are perks in the game that help you in defending the core. All have their plus and minus, but there are some that stand out. At first I didn't like this idea, but I started to like them, and now do. I know there are some you just don't use while by yourself though, but that changes when in a group. So you will see some perks that may make no sense, until you are in a team. Replay-ability comes in the form of having (currently) 5 characters to choose from. With each having unique traits, it's a different style you have to utilize. You can play through as SiMo, then go through as Haigen, each being vastly different than the other. You also have the different secondary weapons you can choose from as well as perks to utilize. All this will also affect what towers you will be taking to support yourself, though it may only be minor. Then there are the Feats of Strength that will ramp up the difficulty quite a bit.
If you are into Tower Defense and/or FPS, this game may be one to look into.
My Favorite Character is Sweet due (aside from the REX) to her ability to catch things on fire. (Splash Damage + Fire = lots of things, well, on fire.

Ain't nothing like setting a packed group of things on fire with a single rocket.

) Her superb air control is useful to get around well on maps and to get out of a bad situation (or for me in some cases, get into a worse situation

).