Hi Pamela
I don't know the Mandalay Inn either but as you can see on this map
Map - Siem Reap Cambodia
the old market area is right in the thick of things, so yes a good area as everything's very close by. I stayed about a 10 minute walk away at a GH in the Wat Bo area myself.
The riverfront in Phnom Penh is also the main upmarket tourist area so you should be fine.
I agree with everything scotters said...good info. The tuk tuk driver I used was knowledgeable and friendly but didn't come into the temples himself...he had to wait outside and we joined him for lunch etc. I'm rather allergic to organized guided tours but a proper guide might not be a bad idea to get the best out of your visit. Failing that you can buy a decent guidebook about the temples.
I travelled with some friends for part of the time but was also on my own for some of the time. I wouldn't walk about Phnom Penh too much on your own late at night if I were you. During the day you'll be fine in both SR and PP, just take the usual precautions.... beware of scams, pickpockets etc.
You'll find that hordes of kids constantly try to sell you postcards, counterfeit LP guides, souvenirs, coca cola etc.... much more so than Thailand...but they have to make a living I guess. Keep an eye on your belongings though. I know someone who managed to get a bracelet nicked by clever little fingers on the beach in Sihanoukville!
The Tuol Sleng Genocide Museum (AKA S-21) is an absolute must. You'll probably come out in tears though....even the birds don't seem to sing in what was once a school playground. More info here.
Tuol Sleng Genocide Museum - Wikipedia, the free encyclopedia