Well, this is very late, but I'm going to talk about Brand New Day, the Spider-Man storyline that made me lose interest in getting Spider-Man.
BND started earlier, with Civil War. In Civil War, Spider-Man, siding with Tony Stark and being pro-registration initially, decided to show his support by revealing his secret identity to the world. This led to a lot of problems, the most important being that an assassin working for the Kingpin ended up shooting his Aunt May, coming close to killing her. Somehow, nobody in the Marvel Universe could save her from a gunshot wound, including Dr. Strange, Mr. Fantastic, Tony Stark, or even Dr. Doom or villains, he asked everyone he possibly could before giving up. Then Mephisto shows up. Mephisto decided to make him a deal. He would bring Aunt May back if Peter gave up his marriage to Mary Jane. Peter and MJ agreed and then the world forgot Peter was Spidey, he and MJ never married and Aunt May was never shot.
In the Brand New Day, there were a lot of new villains, like Menace (the Gray Goblin wannabe), Freak, a new Kraven, Mr. Negative and Paper Doll, as well as having some old enemies like Hammerhead. In general, it was meant to be a return to old Spidey with him having money problems, girl problems and just being in over his head.
Different creative teams every month. Now, at 3 issues a month, it meant that there were 3 issue story arcs that lasted for a month and then the next arc began. Some were pretty good, and I enjoyed them. Some were pretty darn bad and some were awful. The main reason that happened was because it wasn't consistently done by the same creative team. Different artists from month to month will be weird, but manageable. The artist is important, I realize, but doesn't affect the story nearly as much as the writer. What the writer does is really set the tone and the mood as well as tell the story. Two writers could get the same basic concept, the same artist and make stories that feel completely different. Two artists could get the same script and make it feel different, but not too different. Sure, the art matters, but much more than the art, the story matters, and with a different writer every month, it feels really awkward.
Harry Osborn. Now, I guess it's been explained what happened when Mephisto changed things, but it really doesn't make much sense to me that Harry returned from the dead. Sure, it's comics and people can return all the time, but this was more like he died, people were sad and then a few years later, he shows up and it's like nothing ever happened. Apparently he just never died and was in Europe. Or something. It's pretty stupid. Oh, and because of the memory wipe of his identity, I really don't know how he would have died in the first place. How does Harry remember when he almost died as the Goblin? Because what happened before One More Day and BND was that he took a new Goblin formula, fought Spidey, and during a final fight, he paralyzed Spider-Man and set the house to blow up. When he realized MJ, his wife and his son were still in the building, he flew to them and flew them out. MJ was furious that he left Spider-Man inside, and realizing Peter was his friend, goes back in and saves him. Unfortunately, the formula is unstable and kills him. So what now? He just went back in to rescue his enemy who he fights for no reason because his wife's friend/his ex-girlfriend said to rescue her friend. Because they weren't even married any more, remember? Ughh. It's just stupid.
Merging the three comics into one. Now, when there were three different Spider-Man series, I could get all 3 and not feel guilty because if one started to suck, I could drop it and still get my Spider-Man fix. I personally liked Friendly Neighborhood Spider-Man and Sensational was fun, with Amazing being the one grounding them in current continuity. They were different Spider-Man books with different feels that all worked. When they got merged, then suddenly to keep up with Spidey, you had to get three books month and if one was bad, the next month could be good, so you would keep getting it. It got really frantic because, well, let's compare it to Deadpool Team-Up. They both have a different creative team every month, but Team-Up is limited to one issue, while ASM has three, and Team-Up is loosely tied to continuity while ASM is right in the thick of it. Team-Up is easier to deal with because the stories are lighter and limited to an issue every month, while ASM had much darker storylines, engrossed in continuity with three issues per month, giving you no breathing room in between stories. Having lots of different Spider-Man comics means you can read lots of different storylines at the same time, but not get overwhelmed by any one storyline, whereas with one tri-monthly, they hit you with it and hard. Oh, and you are specifically limited to three issue storylines. Most creators have more leg room, but they have to make it exactly three issues.
In closing, I'd just like to say that I tried BND for a bunch of months, but just stopped caring with the really bad new villains and just hating all of the stupidity of the deal with Mephisto leading into all of it.