Yeah, as great as some of the shots and moments in Spider-Man 3 are (Birth of Sandman, the symbiote in general, when Spidey is falling through the debris while trying to save Gwen, etc.), I have to say that overall, the effects in the movie are quite fake a lot of the time. There are some very unrealistic shots, like the aforementioned head replacements on Spidey (when falling and fighting Venom, but also when making the cage of poles around Venom at the end, very bad). One shot that always stuck out to me was the shot when Spidey jumps out of the window after "Go get 'em Tiger?" That shot is so...bleh...no good way to describe it. Just makes you sick when you watch it. And there's all the other moments, certain shots with Sandman, a lot of the Harry vs. Peter in the beginning, etc. Overall, the effects of Spider-Man 3 are good and cool, but a LOT of shots don't look too realistic. Compared to the effects in Spider-Man 2, one must consider the work and effects done. For Spider-Man 2, we needed tentacles, and the occasional CG double for Molina. For SM3, we needed the symbiote, Venom, Sandman (with full transformations), CG doubles for all villians, not to mention a lot more complex shots of Spidey without his mask. Just by simple workload and effects needed, one should expect SM3 to be too big to have the effects look too real, no matter if the budget is $250 million. Plus, SM2's budget was only about $50 million less.
In the end, the effects of SM2 were extremely realistic and well done, but overall more simplistic and less challenging than SM3, which still has great moments. But even SM2 had ugly shots (in the end, when he puts on his mask and jumps off the crane, a (very) few shots during the train chase, etc.). Anyway, yeah, the effects could have been better, I think, just not with the given circumstances.