@Sage
I definitely want to see what's up with the Rachni. I enjoyed talking to that asari on Ilium and thought it was a nice affirmation of Holly's decision to let the Queen go in ME1.
I also want to know what's up with the Geth. Holly re-wrote the heretics, as she believes the Geth could be invaluable allies in the war against the Reapers. She also finds Legion incredibly fascinating. She brokered for peace between the Geth and Quarians. Holly believes if both sides took the time to try, they could peacefully co-exist.
The fate of the Krogans and the genophage cure. Wrex is currently in charge in Holly's game, so I'd like to see what he does leading a united people.
What's TIM going to do now that Holly has turned her back on him and blew up the Collector base? For some reason, I see him becoming a problem later on.
In Moira's game:
I want to see what TIM does with the Collector Base, first of all. I'm also curious to see how her continuing to work with Cerberus will effect things in ME3.
I know a lot of us dig the mysterious and sexy british sniper, but I kind of hope that these things occur in ME3:
No new squadmates (except the return of the VS or Wrex). The reason I want this is because I feel as if most of ME2 was about building up our main team, the people who are going to stand with our Shepard when the sh*t really hits the fan. If they died in the SM, well, they just won't be there. I'd also like to see more conversation with them, further development of their personalities and current romances given a lot more attention (especially the VS!).
Lots of chances to respond to situations with our Shepard in various ways. As in, I don't want to see my Shepard act like a block of wood. Give me the reins more. Let me act like the hero or a total b*tch, even if the outcome will be the same... let me choose how to get there. More stuff where we can express how our Shep might feel (like in LotSB, or one of Jacob's romance conversations).
I also hope to see them handle the "starting at level 1" thing in a reasonable fashion. We had the big dramatic death and destruction of the Normandy. I doubt they would do something like that again.
Anyway, that's just me rambling on about my thoughts.

"Damn, Aislinn...will you shut up, already?"