If you like Sci-Fi, play Mass Effect, beat it, and then get this game. You will not regret it.
I will give you fair warning that when it comes to the plot and characters, I will be fairly ambiguous. To be specific would be to spoil the story, and so I will avoid that at all costs.
The most important component of Mass Effect that strangers to the trilogy should learn about is the persistent, player-driven storyline. From the very first level in the first game until the resolution of the second (and eventually the third), any noteworthy decisions made by the player not only define the outlook of their protagonist, but determine in many ways, where their path will take them going forward. The developer Bioware uses a unique and interesting approach of subtly cataloging player decisions to determine what missions and NPC interactions will present themselves in the future, even what characters and NPC's will appear from one game to the next. At the start of Mass Effect 2, a player who imports their protagonist (hereby referred to as 'Shepard') from the first game is reminded of how major events unfolded in the previous installment and is given a brief summary during character creation (as the player is given the choice of changing the appearance of their Shepard at the beginning of Mass Effect 2). From there, the epic adventure on the Final Frontier begins. And just like in the first game, the player will be presented on a regular basis with opportunities to effect the fates of their team and crew members as well as their own through their actions or lack thereof.
I won't be giving a summary of the plot, not only because it wouldn't be in good taste, but also because outcomes are very much dependent on what the player does and the order of events can vary greatly. Finally, there are other sources (i.e. masseffect.wikia) that could supply that information. Suffice to say that each of the characters (besides Shepard) have very much so their own unique and carefully crafted personas, encompassing a widely varying spectrum of morals, motives, and backstories. You won't find dime-a-dozen, summer action-movie characters with cheesy one-liners, or heavily stereotyped heroes and anti-heroes so popular in more shallow narratives (not that the aforementioned don't offer their own brand of entertainment). From the first dialogue, it is plain to see that Bioware spent a very long and intensive process selecting voice-actors, writing and revising scripts, and sculpting a unique and memorable supporting cast, which would constitute an indispensable building-block in the Mass Effect story. Losing a team member along the way might seem trivial in other games, but in Mass Effect 2, you might just genuinely miss them, and so the player becomes, as Commander Shepard should be, conscientious of the well-being of his/her crew.
As far as gameplay is concerned, it has certainly evolved drastically since Mass Effect. The player is much less worried about balancing their precious talent points between abilities and more mundane attributes (i.e. weapons skills, armor) simply because weapons are no longer talent-based and armor is universal to all character classes. Several RPG die-hards will probably be disappointed with the change of Mass Effect's formula, but I say that they need to be more open-minded as to what constitutes a role-playing game. Some things are simply frustrating or overly complicated, and no amount of tradition makes it worth keeping. 'Oh no, what would we ever do without an annoying overflowing inventory like a swollen bladder?' That said, yes Mass Effect 2 has a bit more of an action bent than Mass Effect did (what with 'reloading' and an effect cover system). But what Bioware realized and what everyone else SHOULD realize is that gameplay and narrative do not come second to adhering to strict genre archetypes. Blurring the lines between RPG and third-person-shooter (whatever the hell you'd like to call it) needn't be horrifying if you can see how much it simplifies and improves the flow of battle. That is all I have to say about that.
Difficulty is extremely well executed. For those who simply want to revel in the narrative and have fun killing things, normal should strike a great balance. Harder difficulties progressively add layers of complexity to battles with more and more enemies gettings shield and armor, requiring the player to think very carefully about who to bring on a given mission and what weapons to employ. As with Mass Effect, the player is always accompanied by two team members of their choosing on a given mission (although there are a couple minor exceptions). Speaking of missions, the perspective buyer should be happy to know that each extra-vehicular activity (EVA, as in, getting out of your ship and doing something interesting) is now carefully crafted and unique, whereas Mass Effect EVAs involved driving around eerily repetitive, sparsely populated, boring worlds in your occasionally amusing, but not-enough-to-break-the-monotony Mako, looking for more rocks than even the most passionate geologist would care to count.
As far as appearance is concerned, the game is positively gorgeous. Especially-so on PC. The graphics options really provide the ability to portray this space-epic in gloriously rendered awesomeness. It's even easier to appreciate how wonderfully crafted the lighting is when it is reflecting off your gleaming, fully-customizable armor. I will happily admit that I have spent hours tweaking the sliders of my Shepard's features, and colors and varieties of his/her armor to achieve what I thought was a good look. Character appearance has come a long way since the first installment and it really isn't difficult to make a character that kicks ass and looks the part.
Finally, this time around the PC version isn't a port, but a separately developed platform. PC gamers (myself included) can rejoice in having a fully functional, keyboard mappable, and wonderfully crafted version for their platform. I own the PC version and there are no issues worth putting words to really (any major issues were quickly patched and are no longer relevant).
All in all, Bioware completely outdid themselves this time around and although I never thought it would have been possible, I am even more psyched for the final installment. Welcome back Commander!