So what significance does the empty house have in a chart? For example, most of my "activity" is in the 9 through 12 houses, and having a lot of Aqua, and nothing in 5th, I sometimes feel the lack of love/affection/familial stuff..

My understanding of empty houses is that the energy of the planet ruling the sign on the cusp is what you take into consideration.  I hope someone with more knowledge here responds because I am interested as well. 

But what if there are no signs on the cusp and no planets in the house? I have a lot of houses empty and not quite sure how to look at it. The only thing I can think of is that meeting people who have those houses filled should compliment me and vice versa?

There will always be a sign on a house's cusp.

If you use equal houses, then the new cusp will always be 30° from the last.  (Example, my asc is 16° Cancer, so in equal houses the cusp of the 1st is 16° Cancer, the cusp of the 2nd 16° Leo, 3rd cusp 16° Virgo, etc. etc.)
Placidus (the default at astro.com) is quite a bit different and I don't know the exact method for how the cusps are calculated.  Thankfully, I got into astrology after charting software came along.    If you look at the details table of a chart on astro.com, it will tell you what sign is on the cusp of each house.

A lot of people have empty houses.  You are not alone.

Houses are like settings, planets are like actors.  So the empty houses have fewer scenes then the regular sets in the soap opera of your life, BUT...eventually something will transit those empty houses and you get to shoot on location.

notatirem- I always love your explanations!

How do you know when something is transiting your house specifically? I am only recently starting to piece together the astro energies to my own feelings/life.

 For example, moon is transiting Capricorn these last few days (i think thats right) and I am having a challenging time with some situations. 

How much of it is the influence of planets and how much my own lessons and behaviors? Also, how can I find out more about my pluto/saturn relationship? My understanding is Pluto is in Cap this year and leaving Cap sometime at the end of 09 - how does that affect us, or me?

Thank you notatirem for the explanation - I think I had a skewed understanding before.