As for Mass Effect 3, I have faith in it. The gameplay is gonna probably remained unchanged, save for a few tweaks and probably a fusion of Mass Effect 1 elements, which is great in my opinion. However, they can royally fuck it up in 4 different aspects. I'll go in order of severity, from least problematic to most.
1) The music: 1 and 2 had great music and this new composer doesn't seem like the right fit. I'd like to see a blend of some of the techy tracks of one and the sweeping orchestral tracks for 2. Long story short, make it loud and triumphant when needed, and quiet and mysterious when needed.
2) A bad ending: They've already said that ME3 is gonna end different ways depending on what you did over the three games. That makes perfect sense and I welcome any of that. However, there better be a good ending attainable. Maybe not good in a sunshine and rainbows way, but in a meaningful way. Also, no unneeded drama please.
3) A total FUCKUP of the canon: BioWare wrote themselves into a corner, that's for sure. You're going to face insurmountable odds in this game, so I fully expect some sort of deus ex machina ending. That's fine as long as they draw from some of the hints they've placed into the lore of the universe (The Leviathan of Dis, Klendagon Rift, the planet of Klencory, seriously look those up!) However, if they just make something stupid up, it'll cheapen the game beyond measure and ruin any semblance of story they've crafted over the past 4-5 years. Also, the Reapers CAN'T just attack Earth. If they're supposed to be proficient at galaxy-wide genocide, they're not gonna all hang out on Earth while you come and kill them.
4) NEW CHARACTERS: If there are more than 2 extra squad members in ME3, it will be INSTAFAIL. There are a total of 16 members to pick from over the two games, not to mention a METRIC FUCKTON of familiar NPCs that could fill the role (Feron, Aria, Captain Anderson, etc.) Regadless of the possibilities of Mass Effect 1 and 2, ME3's cast should be comprised of familiar faces PERIOD. Hell, the second game spent very little time dealing with the overarching storyline and ONLY focused on the characters. 12 characters was too many also, 6-8 is the magic number.
If BioWare staves all of these problems off, prepare to enter the Bone Zone.