A missed opportunity.
Let's just take this step-by-step.
1.) The much-heralded "new" dialogue system. The conversation system in Mass Effect was hyped to be this total re-invention of RPG dialogue systems. By giving the player multiple abbreviated conversational "tones", you could steer the conversation naturally, without getting buried reading your own dialogue options and instead just going with a briefly described tone of speech, and watch the drama unfold.
In reality, the dialogue system in Mass Effect is a re-skin of everything we've seen before in Bioware/Black Isle-style RPGs. Instead of scrolling through numbered dialogue lines, you point your mouse in one of six different directions to select your response. Your character's options are incredibly barebones and lack any distinct personality beyond the goody-two-shoes responese (hint: press up!), the dastardly villain responses (hint: press down!), or the indifferent (hint: the middle choice!). These directional queues are the same throughout the entire game, and regardless of which "tone" you choose, it hardly changes anything you see unfold in the game.
This does a few bad things to a RPG. A.) Your boring personality (especially the monotonous male lead voice acting ... allegedly the female lead VA is better) makes it boring to play this character. B.) It kills any replayability b/c it doesn't matter if you play as a villain or as a bad guy, aside from minor skill points associated with your morality. And C.) It still doesn't feel realistic! It's a new skin on an old interface. You can still ask the same questions over and over and get the same identical lines barked back at you. You always direct conversation like a private detective, poking topics and listening to overwritten stump speeches blurted back at you, sometimes filled with awkwardly in-depth amounts of history and game lore thrown in just to get it in there somehow.
2.) The death of interesting tactical RPG combat. If you've played any of the Infinity Engine RPGs by Bioware, you've seen how awesome group-based tactical combat can be. Real bosses present a real challenge and hard-earned rewards. Any of the dragon or lich fights from Baldur's Gate II are reason alone to miss the glory days of experimenting with combat tactics until you finally break through and find something that works against a boss. Or even just large groups of bad guys could be a blast to take down, pushing you and your characters to the limit, using all of your abilities to get by the skin of your teeth.
But then KOTOR came along. While KOTOR was a fantastic storyline to play through, it wasn't exactly the most balanced gameplay ever. As soon as you got a group of Jedis, you could plow through the entire game on autopilot. The difference between Mass Effect and KOTOR is that you can plow through the entire game on autopilot AS SOON AS YOU START A NEW GAME. Combat is absurdly simple. Point and shoot. Take cover. Or don't take cover. It doesn't really matter. You'll cut through everything with nary a problem. A few boss battles offer a minor, minor challenge in that at least it's more than just aiming and killing until they're dead. Instead, maybe they move around faster, or maybe you have to shoot some spawns first, then shoot the boss ... etc., etc., etc.
Suffice to say, if you enjoy tactical combat with any challenge whatsoever, you won't find it in Mass Effect.
Sort of a tangent to the easy combat, don't expect any interesting class building. You're either shooting a gun, using a few Force-like powers, or some combination of the two. Whether you play a Soldier or a Sentinel or whatever, it doesn't really matter. The game will play basically the same. So there goes that element of replayability. Also, don't expect gear upgrades to be anything to look forward to. Everything fires and feels the same. You never feel "more powerful" with new items or noticeably more empowered. All gun styles fire the same, so if you've fired one assault rifle, you've fired them all.
3.) World lore, characters and storyline progression. This is the big one, one that Bioware usually knocks out of the park. If you're playing a RPG for any reason, at the very least you expect a good, epic, emotional storyline to get swept up by and see interesting places and meet interesting characters. You'd think with an original IP, Bioware would have this down like science. ... Which, in a way, they did turn it into science. The world and lore of Mass Effect is incredibly academic and clinical. The narrative is usually delivered in long-winded monologues by NPCs with varying quality of voice acting. It's told like a college history course lecture. "THESE PEOPLE DID THIS TO THESE PEOPLE, THEN THESE PEOPLE DID THIS OTHER THING TO THOSE PEOPLE, THEN SOME OTHER PEOPLE DID ..." It's semi-interesting stuff, more in line with what Lucas did in The Phantom Menace. Lots of overarching economic and factional disputes. Race wars. Foreign threats. Stuff that happened in the past.
Maybe it will capture your imagination. It didn't capture mine.
The manner of storytelling is like a textbook, rather than anything unfolding before your very eyes, or discovering yourself through your own actions, or learning anything from your environments or world design. No, all that stuff is pretty plain and ordinary. A sci-fi RPG filled with corridors and hallways, elevators and switches, blandly industrial complexes that could be present-day Detroit ... or intergalactic spaceways of the future. Whichever.
Which is odd for an RPG in particular, a genre where the player is accustomed to directly affecting the course of the storyline and directly being responsible for whether civilization survives or crumbles. In Mass Effect, I never felt this way about anything that was happening. Instead, you're just privy to hearing about or watching stuff happen, more of a bystander or a loosely involved tangential player, watching cutscenes go by as you plod along the linear gameplay straight 'n' narrow.
All in all, I was expecting a lot from Mass Effect and very disappointed once I actually played through it. The game sets the stage for two sequels. I hope the sequels will spend more time directly telling stories that directly involve you, the player, and you'll spend less time listening to history lessons and monologues. I hope the sequels give you meaningful choices to make throughout the game, more than just a couple token "kill-this-person-or-this-person" choices, and offer more replayability through branching storylines and more nuanced combat and class play styles. But ultimately, I hope Bioware raises their game when it comes to story and character development. Rediscover their sense of humor, originality and human-ness. The plot and characters in Mass Effect are sterile, streamlined and edited down to a perfect approximation of a good RPG, but takes no risks in originality or creativity or surprise.
Oh, I will say one thing nice about Mass Effect. The score and original music is AWESOME. A real Blade Runner vibe. It's perfect.