Best site to purchase skip-the-line tickets?

Your question is a little hard to answer. What specific sites will you be visiting? Vatican? Roman Forum? Borghese Art museum? Uffizi in Florence? You need to state in your questions cities and sights for anyone to give you information. What cities are you visiting, what sites?

In Rome - the Colosseum, Sistine Chapel, St. Peter's Basilica, Trevi Fountain, & Borghese Gallery. I have read in the RS travel guide that it's best to not buy the tickets on line for Colosseum and to buy the 3-in-one ticket at Palatine Hill for that.

In Florence I plan to see the Academia, Ufizzi Gallery, Ponte Vecchio, Boboli Gardens.

Laura, a ticket for the Palatine and Forum includes the Colosseum regardless of if you buy it from the official site or at the Forum or Palatine.

Online:
http://www.coopculture.it/en/the-colosseum.cfm

A ticket bought in Rome or online allows you to skip TICKET lines but not security check queues.

Vatican Museums/Sistine:

I'd recommend the three-hours tour which includes the basilica as it allows DIRECT access from the Sistine into the basilica: no waiting in a second queue and 2nd security check. It hits the highlights, and once the tour wraps up (in St. Peter's) you're free to spend as long as you wish in the basilica on your own. You will have to choose a specific time/day.

http://mv.vatican.va/3_EN/pages/MV_Home.html

This tour:
https://biglietteriamusei.vatican.va/musei/tickets/do?action=booking&codiceTipoVisita=74&step=2

(Editing to add: because the basilica is free, there are no skip-the-line tickets for entering via the main entrance.)

Galleria Borghese:

http://www.tosc.it/tickets.htm?affiliate=T2C&sort_by=event_datum&sort_direction=asc&fun=erdetail&doc=erdetaila&erid=912678&language=en

You need to choose a specific time/day for this as well, and need to be there 30 minutes in advance of your time slot. Just about everything on you will need to be checked in the cloakroom although you're allowed to keep a camera. I think you're also allowed to keep a phone but it must be turned off.

Trevi is outside, in a piazza, and is just a walk-by: no tickets.

Uffizi and Accademia:

http://www.b-ticket.com/b-ticket/uffizi/default.aspx

I wouldn't bother with tickets for the Boboli Gardens as lines are not long at that one: just buy them at the palace (Pitti Palace):

http://www.polomuseale.firenze.it/en/musei/pitti.php?m=palazzopitti
http://www.uffizi.it/index.php?en/238/il-giardino-di-boboli

Ponte Vecchio is a walk-through: no tickets.

We were in Rome last year and used the Roma pass, it is good for 3 days with entry skipping lines at the colosseum and gives you entry to many other museums. It also gives you a 3 day metro pass. You can get it there at any tobacco shop, which are all over the place, so you can purchase it when you want. It also had a good city map included..

Rick's guidebooks would also direct you to use each attraction's own web site, as Kathy provided above.

Doh! Thanks, Laura. I forgot to mention that the links are for the 'official' ticketing sites.
A note about the Roma Pass:

A 72-hour pass is 38,50 € and covers ticketless entry (you still have to go through security) to any two of the attractions it covers. For everything above the two choices, there's only a discount. It also covers use of most public transit within the city of Rome but not trains to/from the airports or some other restricted urban trains. It also doesn't cover the Vatican.

Whether this is a good buy for you depends on what else you might plan to see, and how much you may intend to use transit. Tickets purchased online for the Borghese and the Colosseum/Forum/Palatine are running about 15€ and 14€ respectively (the latter is 12€ if purchased in Rome without reservation fee). Individual tickets (BITs) for public transit are 1.50€. There are also 24-hour (7€) and 72 -hour (18€) transit passes that cover roughly the same parts of the transit system as the Roma Pass.

We've only used transit maybe 3-4 of times over a couple of trips, and one of those was an FL train that the pass wouldn't have covered but you may use the system more than we did. Anyway, it's a matter of doing the math? Some travelers like passes for the convenience whether they break even on them or not.

Oh, if using the pass for the Borghese you must still make a reservation, and it can only be done over the phone.

Florence has a 72-hour pass too: Firenze Card (no transport) and Firenze Card + (includes transit). Those are 72€ and 77€ respectively, and there's no limit to the amount of covered attractions you may access ticketless during the life pass. The challenge is cramming enough of those into the 72 hours to make it worthwhile. Florence is compact enough that we've never felt the need to use public transit there.

Wow. Kathy and Laura, thank you! I have a lot to think about. Your posts were VERY helpful. I really appreciate the time you took to explain and help me out!

Kathy,

The link to the tour had an error on the page. Pink box: "An error has occurred. It has not been possible to perform the request operation." Gray box: "Reserved area for Tour Operator with accreditation."

When I go to the site without the link I don't see a tour that includes all three, vatican museums, sistine chapel and St. Peter's Basilica. Should I book the vatican & sistine tour and then that will include St.Peter's?

And we plan to walk to everything in Rome. We will use the train if/when we are exhausted. :)

Laura, is it the link to the Vatican Museums that isn't working? That one can be sticky for some reason when copy/pasted. Try this:

https://biglietteriamusei.vatican.va/musei/tickets/do?action=booking&codiceTipoVisita=74&step=2

Not sure what pink box/grey box in which link you're talking about.
Let me know...

Note that the Sistine Chapel is inside the Vatican Museums, not separate from it, and one ticket covers both.