Every house is different. If you have forced air heating and cooling, sealing the duct system (including boots, plenums, equipment boxes, etc.) is probably the best thing I've done in terms of bang for the buck.
I'm just an amateur but have asked myself the same question for a looong time:
1) Orientation of the house is a big factor, though something you may not be able to change. When the sun hits, and how much, dictates a lot of heat gain or loss.
2) Air sealing is a sleeper issue. Important and easy to overlook. Costs very little for materials, but labor and testing could be expensive. But in my region (hot-humid), the amount of air infiltration is a big factor.
From what I understand, insulation does little good if you have an inherently leaky building envelope. This is attested by some of my experience adding insulation and seeing little or no payback from it. In hindsight I should have paid more attention to air sealing, that was far bigger than I thought.
As is often said, a lot can be learned by purchasing a license for HVAC-CALC at the top of most every screen on this site.
If you plan on making the envelope "air tight", you need to pay careful attention to alot of other things or you may end up w/ huge problems.
Some things like:
make certain the a/c is sized properly or you will end up with growth
you will need some type of fresh air exchange
be careful to watch for natural draft appliances and you house pulling into a negative pressure.
Yellow Dot, you make some good points if this is carried to really tight air sealing:
>>you will need some type of fresh air exchange
Yes, I completely agree for a house which is objectively tight. However I was thinking also of going from a loose leaky house, to a position closer to the mean, and that might not necessitate engineering a ventilation system. I shoulda asked if this was indeed the case.
>>be careful to watch for natural draft appliances and you house pulling into a negative pressure.
Again I totally agree. If your house gets a significant negative pressurization, all sorts of bad things can happen and this is one of the most dangerous. If the house is in a hot-humid climate such as mine, far better to run the house with a slight *positive* pressurization. In a cold climate, better to listen to Lstiburek than to me.
>>make certain the a/c is sized properly or you will end up with growth
Is it not gospel to size the a/c properly, tight house or no? Mold growth is indeed something to be very respectful and cautious about. Based on the case studies I have heard however, there are factors far more significant than being a tightly built house. Would you agree?
I design homes that have utility bills 35-50% less than standard code built homes. They have to be designed from the ground up in a "systems approach" method. This provides the most benefit for the least amount of initial cost. Homes also have to be designed for the climate they are in. Along with lower utility bills, I also design in comfort, humidity control, indoor air quality, and durability. All these things can be done for little or no cost over code construction. Two good sources for this information are DOE's Building America site and buildingscience.com
The worst thing in the world is a "passive means of ventilating a home" We have millions of those now, and they don't work properly. The best way to build a home is to build it as tight as economically possible and then mechanically ventilate. When you can mechanicall ventilate a home for $300.00 there is no excuse not to.