While I don't think that Spider-Man 3 will be the LAST great comic-book movie per se, I think it signifies the peak of the CBM genre. Now, I don't mean to say that Spider-Man 3 will be better than The Dark Knight, because that's like comparing apples to oranges. They're two different storylines about two different characters in completely disparate atmospheres. What I mean to say is, looking at the big picture of comic adaptations, we're nearing the midpoint of the genre's cycle.
Everything in pop culture goes in cycles, and the comic-book movie genre is no different. The Superman series started off grand, but doomed itself with III and IV. Same with the Batman series: started off great, and to much acclaim from both critics and fans, but then shot itself in the foot by putting nipples on the Batsuit (among other things). After Batman & Robin, the genre was more or less dead. Enter Brian Singer.
Singer saw through the smoke and flash of previous superhero movies and distilled the X-Men series down to its essentials: characters and morals. Finally, we had a superhero movie that remained true to the spirit of the source material. The only thing that stopped X-Men from being a worldwide smash hit was the minute budget and rushed release date (thus began another trend: 20th Century Fox's preference for bright lights and explosions in place of character development and substance). Despite the stigma of the superhero genre, despite the efforts of the studio to kill the movie quickly and quietly, he succeeded in showing the world that a good CBM could still be made. So what happened next? Sam Raimi's Spider-Man, which not only reinforced the notion that good CBMs could be made, but that with a higher budget, they'd make more money. The genre exploded. Within 3 years, we had Hulk, X2, Spider-Man 2, Hellboy, The Punisher, Daredevil, etc. etc. Studio audiences ate them up. As a general studio rule, if it was a CBM, it'd make a sh_tload of money.
So now we're looking at 2007 and beyond. For the sake of argument, let's say that the X-Men and Spider-Man franchises end after 3 movies. Okay, there go the two leading series in the genre. What are we left with? The Dark Knight, which promises to be awesome, Fantastic Four & The Rise of the Silver Surfer, which has average expectations (especially based on the first installment), and MAYBE a sequel to Superman Returns, which wouldn't be a bad movie by any means. These are just the "big" superhero series. We'll see Wolverine, Captain America, Iron Man, Wonder Woman, The Incredible Hulk, Transformers, Ghost Rider and probably 4-5 other standalone movies in the next couple of years. No problem.
However there's also the start of a depressing trend: making movies that, to be perfectly honest with you, nobody is going to see. Ant-Man. Seriously. Who the hell is going to see Ant-Man? Unless the trailer looks awesome and there is an insane marketing blitz, NOBODY is going to know who Ant-Man is. It doesn't matter HOW big the budget on Ant-Man is, it's not going to bring in even HALF the money of Spider-Man. This is going to be the next phase of the genre's cycle- the studios overestimating its popularity. Studios will just keep pumping out new CBMs because they made an insane amount of money 4 years previous. I have a horrible vision in my head of Ant-Man 3 in 2011.
To sum up this rant:
Spider-Man 3 will be awesome. Then the Spider-Man franchise, much like the X-Men franchise, will be done for 10-20 years. We'll be satisfied for a few more years with the likes of Superman and Batman, plus the odd standalone that might be good (Iron Man, Wonder Woman, etc). Then, the floodgates will open and dozens of STUPID, BRAINLESS, CHEAP superhero movies will be released by the major studios in a ******ed attempt to capture the magic of the most well-known franchises (any proposed spin-off of the X-Men series other than Wolverine falls into this category. Again, who the HELL is going to see Magneto? Not enough people to make Fox any sort of money.)
We're not even close to the end of this cycle of the comic-book movie, but I believe we are at high noon.