Originally posted by: ergeorge
I'm in the middle of it right now.
Not a whiole house, but a 1400 ft^2 addition to my existing house.  At present, it's closed in (roof on, windows & doors in, stucco lath applied), and I have most of the DWV plumbing done and about 3/4 of the supply plumbing.
A few things to consider...
Make an honest assesment of your skills.  Have you done construction work before?  Do you know what things look like behind the drywall?  That's important even in the design phase, or you'll end up designing something that can't be built (or can't be built cheaply).  Also make a realistic assesment of how much time you can spend on this project, and if your willing to have it own nearly all of your freetime for over a year (for a large addition or house).  Is your family willing to make that commitment also?  Do you have friends with any skills who'll be willing to help out on weekends.
Read up on building codes for your area.  Again, before you start designing.  Or you'll spend alot of time on reworking the design to get your plans through the code check process.  Code information can be hard to come by without buying expensive books.  The 
Code Check books provide a good overview, but your local jurisdiction may use something different or may amend the national model codes.  You need to check with your local building office.  Here is an online resource put up by the regional building department in my area: project.
PPRBD
Find an engineer and/or architect that's willing to consult with you on a DIY project.  I'm very lucky to have a neighbor who has a civil engineering business (primarily residential & light commercial).  He's saved my a$$ several times in various phases of the project.  In particular, you will almost certainly need your foundation design and soils report signed off by a licensed engineer.
Plan on spending about 6+ months on the planning/design/permit phase.  I reccomend 
TurboCAD/Floorplan3D for doing the drawings.  I tried several packages, but this was the only consumer level program that I found that could easily produce the kind of drawings you'll need.  Start following eBay for a wide format printer.  I got one for about $60
Come up with a reasonable cost estimate during the design phase.  Multiply it by 1.5  Do the same with your schedule estimate.
Pick your battles.  There are some things that you're better off contracting.  I contracted out pouring the slab for the first floor & garage, for the roof and for the stucco.  I don't have the kind of manpower available to tackle that stuff myself, and it's time critical stuff.  My neighbor has told me that I can contract out the insulation for only slightly more then it would cost for me to buy the materials.  We'll see.
Get multiple estimates for anything you do contract out.  It sounds basic, but when you're stressed out, in a hurry, can't take time from work to meet with them, it's tempting not to.  But I've had some huge differences in estimates from reputable contractors.  What happens sometimes is that these guys will almost never tell you that they don't want the job even if they don't want it (to busy, don't like working with DIYers, job to small, etc.) So they'll just give you a sky-high estimate.  If you're a sucker, they won't mind doing it for that price.  Expect about half the guys you contact not to return calls, and half of the remaining to show up late or not at all.
Have an HVAC contractor look at your plans before you go to get a permit.  Decide what kind of system your going to need.  This is biting me right now 

  The furnace in the existing house is almost big enough as far as BTU/hr is concerned, but the HVAC guys are now telling me that it will be next to impossible to get adequate performance in the addition due to the way the duct work will have to be run 

 
Plan your plumbing walls!  You don't want pipes in the exterior walls (if you live where it freezes at least), and anything that you'll have to run a drain pipe through should probably be 2x6.
Plan ahead for long lead-time items like roof trusses.  Be aware that, in the summer, lots of stuff can be long lead time (floor joists, contractors, etc.), because these guys will take care of their big contracts first before a DIYer.
Consider using an ICF (Insulated Concrete Form) product for your frost wall or basement wall.  I used FormTech.  These are styrafoam forms that stack up like legos, then you pump em full of concrete.  You then have a very strong monolithic, insulated wall that you can easily attach finishing materials to on the inside & out.
Pick a wood floor over a concrete slab.  I thought I'd be saving money going with a slab floor, but it turns out that concrete contractors are more EXPENSIVE then I had anticipated.  It would've been more work for me and about the same amount of cash, but a wood floor is much more comfortable to live on then a slab floor. 
That's all I have time for at the moment.