Deadpool is pretty good when he's offset by a serious, perhaps overly serious character. When they indulge Deadpool too much in the goofy adventures he goes on and there's no ceiling for the crazy, it quickly spirals out of control until it's practically meaningless nonsense. When they stick him with a Cable or Punisher or Norman Osbourne type character, it creates a nice dichotomy.
Reynolds has bad luck with superhero movies, but I wouldn't write him off as Deadpool yet. He was pretty good for the first 5 minutes of Wolverine Origins, and he's got the cocky, quick wit that Deadpool makes use of.
For me this movie will live or die by the plot, which I suppose sounds kind of obvious, but considering that many superhero movies get by on pure character power alone (Iron Man, The Amazing Spider-Man, Thor), I don't think the Deadpool character can carry the film without a solid plot for him to play off of. If the whole movie is just about Deadpool going on a zany adventure with the goal being a lifetime supply of chimichangas (if that's the plot, you all owe me a coke), then fuck it. If they give him a real villain that does villainous things that gets you to really hate him, and Deadpool fights with the villain for a reason beyond chimichangas and because the script called for it, the movie could work.
Things I want from the movie: Hydra Bob.