First, decide if your answer to questions that start "Can I do . . . " is going to be "Yes," or "just a sec, let me check the rules . . . ." Make sure your players know that too. Decide if "Yes" means, in general or just until I've had a chance to do the research.
Second, sit down with a piece of paper. Decide what level you want the party to be when they complete the adventure. Along the left margin of the page, write numbers from 8 to the completion level. Then, sketch out what the bad guys will be doing (barring interference by the party) at each of those levels. Give the villians a goal, and plan out how they're going to get there. In the far right margin, make brief notes about the kinds of adversaries the party is likely to encounter at each level. Sure, you've got the entire MM, but you don't need to use all of it. By picking a thematic set of sub-adversaries, you've taken the first step toward dungeon ecology.
If this is going to be an epic campaign with a specific goal, let the players know that. It will help reduce the feelings of being railroaded into your story. At the same time, at every juncture of the adventure, include at least two, if not four, alternate routes they can use to advance the plot.
I find it helpful to note the effect of chosing each branch. If the party opts for this branch, they get x piece of information, or z useful item. If they don't, the bad guys get y.
Don't screw the party for not chosing the option you prefer.
Don't forget to occasionally give "Go home and recover for a week or two" as an option.
Do think about what the bad guys are doing while the PCs are on sabbatical.
Avoid the SuperNPC. It just destroys the PCs agency within the game. Do plan out encounters in advance. Give the party an option to not take on more than they can deal with. If they do bite off more than they can chew, prepare for the consequences. They could be captured, they could be left for dead (and subsequently stabilized by an unknown ally). Someone (perhaps a powerful cleric who can't otherwise get involved) could be so interested in seeing them succeed that he or she will pay to have them raised (but maybe only a limited number of times). But don't let them think that they can take on anything because Mr. Constructor will save them. If you really are worried about this, create a magical item that "stores" one (or some other number) hit point and lets PCs heal level+4 hitpoints as their natural healing. It's cheesy, because it elminates the death penalty. Use it like this: when a PC hits, -9, he appears dead. Unless the bad guys are taking the time to destroy bodies, he's just unconscious, stabilized, and in a deep trance. 24 hours later, your 8th level PC would wake up with 5 hp.
--G