I created my new 4E campaign six months ago (and have been playing it biweekly ever since.) I took my cues from James Wyatt's Greenbriar campaign design Dungeoncraft articles in Dungeon Magazine to help create it. I'm very much a DM who uses published modules /adventures as a campaign foundation and then binds them all together with my own mortar and improv skills.
I started by choosing my campaign level length (went for levels 1-10) and a "big" module to be the centerpiece of my design and the climax of my campaign (The Gates of Firestorm Peak.) Using that as my campaign foundation (expecting the Gates to open and the party to enter the Peak around level 6-7,) I then took my cues from the pages of the module that set TGoFP up to get a starting town, and some of the character/village plots that could lead the campaign for the first five levels.
Some of those things in TGoFP included a supposed "curse" upon the village, the animals around the mountain going aggresive, a vein of transparent iron called 'nephelium' coming into existence inside the duergar mine, the control rods for the Vast Gate being missing, various citizens experiencing manic criminal behavior, Far Realm creatures manifesting out of nowhere, and the Dragon's Tear comet arriving to herald the opening of the Outer Gate of the Peak.
Once I had all these ideas gathered (which came straight from the module), I then went on a shopping spree through all of the online Dungeon Magazine modules I had acquired over the last 5 years (as well as a few others)-- pulling out any modules that might have to do with crazy animals, murderous villagers, the Far Realm, astronomy, weird metal and stuff like that. I probably found about 10 or so modules that all could apply, then I wrote out in bullet-point form the plotlines of those 10 modules, checking to see how many of them were close enough to things within TGoFP that they could be adapted and/or merged together, and a plotline to fill levels 1-5 began to form.
What's nice is that because I already have the modules and the plot hooks are all tied towards the metaplot of Firestorm Peak, I can drop hooks here or there and see what the players pick up. And whatever they do... I have the module right there and then to feed into. Thus there's more options for everyone because at any one time I might have three or four directions/hooks out there to jump into.
Finally... now that I had the all my foundation modules at hand and the hooks to tie them to each other and the metaplot... I just began creating campaign-specific Character Themes (adapted from the Themes I got from the Compendium) that would tie the characters themselves directly into many of these story hooks and metaplot (and thus providing background and thrust to the characters so they remain hooked into the story.)
Thus far it's worked exceedingly well... and I actually have very little I need to do between sessions as everything is already created and sitting there ready to be pulled out at a moments notice (or improvised around if they do something slightly unexpected.)