First I want to say I really really enjoyed ME 2 (I'm 2 completed playthroughs and 2 others started - but I won't continue them until DLC is seemingly all done - mainly the Hammerhead and perhaps Katsumi or whatever the NPC is called), so I hope this doesn't come across as a big anti-ME 2 rant, because I have no regrets whatsoever from picking up ME 2, it's just that every game has flaws.
1 - No main villian. The Illusive Man seems like the closest thing to a villian, since the Collectors are pretty much nameless and faceless, but Illusive Man is (mostly) on your side.
2 - Love interest from ME 1 gets so little attention in ME 2. I understand why they can't be shipmates due to Bioware wanting them alive in ME 3, but in ME 2 it hardly seems they were actually LI's in ME 1 given how they're treated. I think more LI story in ME 2 and some sort of one-time mission where you fight with them would have been just awesome. My Paragon got nothing "good" from Ashley and my Renegade got nearly nothing good from Liara (I ALWAYS will kill Kaiden in ME 1 because I haven't liked that character since Carth did it first), and I feel I would have been less disappointed if the ME 1 LI's weren't even in ME 2 than in their current incarnation. BTW my Paragon will not ever be loyal to Ashley, but my Renegade will always be loyal to Liara, and I'll carry those through to ME 3 to see the story ramifications.
3 - Too many shipmates (and Zaeed is pretty pointless). In ME 1, my soldier always took a biotic and a techie (Liara and Tali), my biotic always took a solider and a techie (Ashley and Garrus), and my techie always a soldier and a biotic (Wrex and Liara) - notice who's missing? There were pretty much 2 choices for each role, and that was good enough. In ME 2, I feel there are too many choices to bring along, and would rather have fewer, but those that were included be developed more. My own personal "useless" list is Zaeed, Jacob, Thane, Jack and Samara (and the choice in her loyalty mission doesn't change anything at all, so it's essentially useless in terms of story - it's just a paragon/renegade booster). I would rather have had Legion earlier and much more "fleshed" out than any of those 5 I listed. Granted, in combat, I find Jack incredibly useful, but her abilities could have gone to someone else. I'm sure others totally disagree with me on which are good shipmates and which aren't, but the point is I could easily have accepted half the ones I like not being there if half the ones I dislike aren't there, also, and ALL the remaining ones had deeper stories. Would have made every remaining one feel more important.
4 - Small Citadel. I just wish I could have visited more of the older areas to see the differences. Not that the Citadel in ME 2 is done poorly, but it's a side-area now, and that just feels weird.
5 - I preferred the ME 1 style health/status bars for your squad in the HUD to the new ME 2 ones. I got used to the new ones pretty quickly, but I still feel that I have a better handle on shield and health status with the old one style vs the new style.
6 - Final fight was very anti-climatic. Probably due to no true single villian, but to me it was easily the weakest part of the whole experience. I think I would have probably preferred (given no single villian) some sort of shocking discovery and decision making conversation/cutscene over what was given, especially since this is the "dark 2nd act", but I guess for those new to the ME world, the game had to have a typical last boss fight or something. But as boss fights go, it was pretty poor, I thought.
7 - No hide helm toggle. Sure it sounds a little petty, but why do game makers have me even make a face if it's going to be hidden? I wear the visor thingy (like a perfectly horizontal 3/4 blue shader) just so I can actually see most of my face while getting some sort of benefit for the head slot. Yet most of my shipmates wear clothes in combat? In general, the customization concept is good, but no matter how much I tweaked, I never really felt like I looked any different. And my crewmates really never looked different (apart from one skinning choice). Surely Bioware has to know that for all of it's previous games (as well as other RPGs like Morrowind, Oblivion and Fallout) that players LOVE cool looking armor, yet there's not any really to choose from in ME 2 (ME 1 may not have had tons of great looking stuff, but it at least had lots of different looks to choose from, especially for squad-mates).
Like I said at the top, I had a lot of fun playing ME 2, and don't regret for a moment buying it or playing. In fact, I probably had more "fun" (in an arcadey sort of way) in ME 2 than ME 1, but once both my ME 2 toons are set up for ME 3 (male Paragon, female Renegade), if I get a feeling in a year or so to play a Mass Effect, I'm sure I'll play ME 1 over ME 2 for that "Mass Effect feel". It may have inferior combat, but it's got a superior atmosphere (even though the Mako most definitely sucks).