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I am aware that this has been discussed before at least once, but I came a little late to the party last time I saw it discussed. Personally, after completing Mass Effect 2, I was instantly seized by the need to play Mass Effect 3, and really, I think that the answers for ME3 are hidden within the previous games. Events set in motion will finally come to a close, and the Shepard story will be concluded. But what, really, does that entail?
Here, I will tell what I believe will happen. I hope others shall see this page and speak their minds as well. Perhaps one of us will be right, and see our ideas displayed in the full glory of BioWare's next masterpiece? Who knows. All I know is that this has been an extremely long introduction, and I should probably just cut to the chase.
As far as storyline goes, all we know for sure is that the Reapers are coming. This likely means that an "ultimate climactic battle" of sorts will occur. Choices made by Shepard in the previous games will probably add new allies and enemies. An example would be the Rachni joining the fight should you have spared the Queen in Mass Effect, or Cerberus helping if you didn't destroy the Collector Base. Obviously Shepard's choices regarding the Council in ME1 would be very important as well even if it doesn't come down to a battle.
Mordin's loyalty quest in Mass Effect 2 potentially could result in a cure for the Genophage, which would drastically alter Krogan involvement. If Mordin were ever to develop a cure, the Krogan would multiply rapidly, potentially creating a Krogan army for the proposed final battle. If the Geth were rewritten during Legion's loyalty mission, they would also be potential allies.
Perhaps my favorite aspect of Mass Effect 3 to speculate on is the future squad. I personally think the following: all teammates from both of the previous games that are currently alive will return. Unfortunately, many people will have deceased teammates, and they could have none alive at all for that matter. Thus, there will obviously be new characters in the team. Who they are remains to be seen, but I assume that not all of them will be unknown. Perhaps Aria from Omega will be one, or perhaps Kolyat, Sidonis, or Harkin.
Also, Cerberus Daily News likely holds more information than most expect. I expect that many events mentioned in CDN will influence ME3 such as the discovery of the Raloi. We may also see key characters from CDN, such as General Partinax. These events will likely be referenced in some way at the very least.
Anyway, this concludes my lengthy speculation. Not everyone will agree, of course, so I invite you all to post your opinions below. Hopefully, this will at least serve for some minor entertainment for you all. Enjoy the discussion!