Having played through the trilogy a few times now, here's my thoughts.
This is the one story BioWare just wasn't able to tell. They get a bit of a pass from me on that, since they've told so many good ones going all the way back to Planescape:Torment. This one just lost its way somewhere and never got back on track.
Plot hole: The "dark energy" killing the suns. Why was that never mentioned again? That parallels the planetary disappearances caused by Lemegeton in the Xenosaga trilogy (which I'm personally convinced the basis for this story was lifted from), but they never come back to it. They could have developed that so the Reapers really _were_ saving organic life by not letting them destroy their own universe.
Star Child: I'm on the fence on this one. I get what they were trying to do (I think). Pretty obvious sexual symbolism for the joining of the Crucible and the Catalyst. The 'child' awakens, sees new possibilities. Conveniently, there's already three color coded pathways built for these choices that StarBrat never saw coming (and he says he tried synthesis before).
Shepard surviving with a high EMS. After the third dream (similar to an old legend of the washing women) we know Shepard is going to die. Have the balls to stick to that. Shepard surviving just undoes one of the best bits of storytelling in ME3. Especially since that epilogue says this all happened long ago, so Shepard would be long dead of old age in any case.
The warped 'dream logic' best summarized by the 'Yo Dawg' post (wiping you out with synthetics). Synthetic life must by definition surpass their creators? Does that mean organic life must by definition become gods? As far as I can tell every race has a pretty strong spiritual belief system.
Dropping the weapon customization system from ME 1. They brought back a bit for ME 3, but 1 was the best of the lot there. Everybody could use every weapon, even if they weren't "good" with it. Also dropping the exploration aspect of the game that riding around in the Mako gave you.
Lack of real choices in ME 3. The 'dialog wheel' was the defining mechanic of the trilogy, but we get stuck with long cutscenes with little to no input and even less effect from whatever lines we do pick. That worked for Xenosaga, because Xenosaga is a cinematic experience - choice was never part of the equation.
Missed opportunity: We find out at the end of ME 2 that everything we thought we knew about the Geth was wrong (and even moreso in ME 3 when we see the start of the Morning War). That could have been developed into a theme where Shepard would be forced to question all the core beliefs of the galactic civilizations, but it never really takes off. I'm honestly not sure what the main themes of the story are supposed to be. Hope? Futility? Courage in a Lost Cause? Overcoming the Impossible?
Obviously I found a lot to like in the series or I'd never have finished playing through it once, let alone several times. Some things just stick out to me though, even more as I see them through repeated playthroughs with supposedly different choices.
I don't have a problem with Cerberus being so prominent in ME 3. That actually follows the formula. The reapers are like Sauron in Lord of the Rings - to powerful to really engage as an antagonist, so you act through proxies: Saren and the Geth in ME 1, the Collector's in ME 2, and TIM and Cerberus in ME 3.