Here are my main sources of dissatisfaction.
The ending. The ending of the game is a disaster. Literally and figuratively. There are three broad failures in the ending.
1- The entire series of games is about choices and the impacts of those choices. The ending is completely canned (i.e., scripted, static), effectively making every decision you have made absolutely meaningless. As icing on the cake, before the end there is a long boring/confusing conversation (with Anderson and the Illusive Man) with multiple dialogue options that have zero impact on the end. It literally doesn't matter what you say.
2- The entire ending is complete gibberish. A glowing leprechaun appears, explains the universe, and gives you three crappy choices all of which result in your death.
3- The final cutscene. No matter what crappy choice you make, you get an almost identical movie that is short, confusing, and explains nothing.
NPC Relationships / Romance. You spend significant effort in ME1 and ME2 developing relationships – romantic and otherwise – with NPC teammates. How utterly disappointing that these teammates (with a couple of exceptions) have so little involvement in ME3. If you happened to choose Liara / Ashley / Tali / Garus as your romantic involvement, you'll be OK. But if you chose Miranda (one of the most popular) / Jack / Jacob, then you are out of luck.
Replayability. If your primary source of enjoyment is shooting your way through the missions, then replaying the game is no problem. But if you enjoy the dialogue, character interaction, and seeing the effects of different choices/decisions, then there is zero replayability. Why explore different choices/decisions when they have no impact on the outcome?
ME3 killed ME2. ME2 was a GREAT game…and I will never play it again. Now that I know that almost NONE of the decisions you make in ME2 have any real affect on ME3, why bother to play it again? If you bought ME3 but never played ME1 or ME2, don't bother. You can view and download a variety of other players' saved games at masseffectsaves.com.
Number of Missions. In ME1 and ME2 there were a number of side missions where you went down to a planet, fought some generic bad guys, and retrieved something quasi-important. While these missions were not a huge deal, they did add some additional depth and play time to the game. In ME3, you just scan the planet and beam up your prize. Boring and makes the game seem shorter. Also gives you the feeling that the developers simply weren't trying.
Mission Interface. In ME2 the mission interface was perfect. The mission was fully described, the steps to complete were detailed, and the mission description reflected the current status. In ME3, in many cases the mission interface doesn't even bother to tell you where to go. The planet might be named but not the solar system. You'd think the 24th century would have Yahoo maps. Having a second computer open with Mass Effect Wikia up fixes the problem, but should that be necessary?
Inventory, Guns, and Weight. In ME1 you could find weapons and buy them in stores. There were tons of weapons. In ME2 every class had very specific weapons they could use, but there were only a few weapons – which disappointed some people. In ME3 there are tons of weapons again, which is cool. There is also a flexible carrying system which lets you customize what weapons you are going to carry based on available weight. Which is also cool. But weight affects power cooldown, creating the unintended consequence of rewarding you for carrying nothing more than a single, very light pistol. In other words, they have added many cool weapons then incentivized you to not use them.
While there are good things about the game (combat, graphics, etc.), each of the good things was a direct import from ME2 (with some minor changes). Very little "good" was added as part of the ME3 development. Many of the missions are great, but the fact that every choice becomes ultimately meaningless at the end means you will probably only play through them a single time.
Overall, the game feels like it was created without adult supervision. It was designed, finished, and rushed out the door without anyone taking the time to play it through and discover the fact that, "Hey, the ending really sucks". This is an unforgiveable management failure. Making sure that products that embarrass the company and infuriate a substantial portion of the customer base don't go out the door is the job of management.
What makes the disappointment worse is that it could have been great. All the elements were there. To get so close and fail…what a shame.
EDIT #1: A quick comment on DLC. Many people are mad about having to pay for DLC on day one. The flip side of this is the Digital Deluxe Version. What a waste of money! This comes with a small robot dog that hides in the cargo hold, a "hoodie" sweatshirt you will never wear, and the DLC included at launch. If I could do it over I would have passed on the DDV and the DLC, and just saved the money. As long as we are going there, I would have passed on ME3 completely.
EDIT #2: I see a lot of people awarding the game high scores, but then in their review saying, "The ending was terrible." That makes zero sense to me. In a normal game the ending is important. In a game that is the finale of a three game series the ending is arguably the most important element. If you were reviewing an airline flight from JFK to LAX, would you say, "We took off on time, the service was great, the flight was smooth...but during the landing we overshot the runway and crashed into a gas station. I'm taking half a point off for the ending, so I award the flight a 8.5!" Probably not.