we just did the package bus trip from Don Det to Siam Reap ($30 USD)... our experience was not good. We were told once we got to Stung Trang they would not drop us in Kampon Chan for the night and then direct to SR as we had paid for...rather they made us go to PP, they stuffed us in a mini-van that normally fits 11 (including driver) uncomfortably.... they crammed in 15 people, and the driver was sitting on another female passenger driving the van. We didn't get into PP until after 10pm, sent to a nasty guesthouse, and then told to be ready at 6am for a bus that we were not able to get tickets on, and ended up leaving at 10:00 on a bus that took another 7 hours to get to SR. Our recommendation- if we did it again... book the package to Kampon Chan, and then buy a bus ticket from there. We are now in Siam Reap, and loving it.

On the same note as above post, I would recommend getting a ticket from southern Laos (Pakse, 4000i) to Kratie and break the journey there. It is a pleasant place to stop, see those dolphins (pretty cool) and buy onward transport fom there. If you try to take the same "ticket" all the way from southern Laos to Phnom Penh or to Siem Reap, my experience suggests you're likely to get "inconvenienced" in some major way and you will inevitebly end up arriving in either of the two places much later than promised. On the other hand Kratie is within reasonable stabbing distance from Southern Laos same day. If you leave Ban Nakasang (town nearest the islands) you will probably be going through the border process around 10-11am and get to Stung Treng around Noon. Then you cross the river and usually have to wait (at the mandatory restaurant stop) for the ongoing vehicle. Last time I went it turned out to be 3 Cambodian boys who looked about 10, chainsmoked the whole way, and and took turns simultaneously working the steering, clutch, and accelerator (no braking required apparently). Rain poured in through the rust-eaten roof and we puddle-jumped to Kratie, arriving about 3pm. Other folks we had seen back at the border and had taken a seperate vehicle were waiting there (for quite some time) for our vehicle which was to take them on to PP. We stayed in Kratie - enough drama for one day indeed. If you try to get to PP or SR same day expect to arrive pretty late and therefore have limited choice of accommodation. IMO Kratie is worth the stop, but Stung Treng isn't (and getting to PP or SR is too much of a 1-day stretch).
Bob, that's great info about booking from 4000 Islands to Kratie. I've been having a really hard time figuring out the least stressful way of getting there. Your advice was very helpful! Thanks!

From Don Det to Kratie should be about $13-15. It really is the best/sanest option if you have time to break the journey. Trying to get all the way from the border to Phnom Penh or Siem Reap in one day is doable, but exhausting and disappointing. This question will arise again and again no doubt.

FLYING?!
Wouldn't it be worth going back up to Pakse and then fly to Siem Reap, or are we missing a bunch then?
It´s $85 but that and the other flight would be our only on this vacation.
Just now in Luang Prabang, from where we will fly to Pakse to visit 4000 islands, and nearby locations. We then want to go to Cambodja, but discovered getting to Siem Reap would be as tough as many of you are mentioning.
So, what do we miss except the ca 55 dollars if we fly? We've just done 8 hours to luang prabang, and I kind of think that those long trips are not the best way to enjoy the landscape - you soon get very tired. Instead I enjoy discovering the landscape on a bike or motorbike locally.
Anyway, what you say about flying?