I have been to DL more than 20 times in my life and have never spent more than one day there. That's not bragging, just the harsh reality of finance, distance, children, etc.
If you go for one day, your per-day cost will be a little higher than when you prorate it out over multiple days. But is still worth it, money-wise.
And yes, you will have to skip some things (just more to come back and see later

).
My personal suggestions (beyond the great tips already offered) for maximizing your single day:
1. Bring snacks in and eat a single large meal in the afternoon to avoid lunch and dinner lines
2. Don't bother with lines for character meets, shows, exhibits, etc. if you have just one day.
3. Avoid Fantasyland and Toontown until after dark, when they thin out a bit, and decided if there is anything there you must ride or just walk through and look around.
4. Decide what side of the parade route you want to be on before it begins or you will be stuck. If you are waiting for the parade (on the east side), send one person at a time through the Matterhorn line (DH rode it 3 times one night that way)
5. If you have only two people, be alert when you get near a ride's loading zone. Sometimes they will call for two people to fill up a car or boat because big groups want to stay together.
All of these tips are dependent on your party being adults, not children. And if it's a big group, you'll always have disagreements as to how to spend your time. I'd either split up right away or put one person in charge so you don't waste time after every ride deciding what to do next.
You can have a great time in just one day; you just have to plan to go full-out the whole day. We have done a single day (with kids) in the off-season and hit all the biggies -- Matterhorn, Space Mountain, Splash Mountain, Big Thunder, POTC, Haunted Mansion, Autopia, basically everything we wanted (some twice) -- as well as many rides in Toontown and Fantasyland.
PHXscuba
"You can't have everything -- besides, where would you put it all?"