In addition to the software we use Skype for talking. It has a nice conference call feature plus I have a phone plan ($30/year) that allows me tie in players with phone access only. Two years ago Skype was the easiest out there to setup and use since VOIP software has continued to evolve. I am not up on the software for VOIP but a google search will have several alternatives.
The experience of using Fantasy Grounds+Skype is very much the same as sitting around the table. Face to face is preferred but if your groups is now scattered across the country it is a more than adequate substitute. Plus if you are fan of the Old School Renaissance and it is not popular in your area you have a means to getting a group to play these
Using VTTs has advantages and disadvantages. The best advantage is fog of war. Most VTTs allow you to obscure the map and reveal portions as the party explore. The next best is the ability to keep a log of what everybody type in chat. However this presumes that you use the chat and not conduct 90% of the session via voice. However even if you use voice the chat log is good for the old trick of passing a DM Note. However unlike the tabletop there is no way the other player will see the note being passed.
One disadvantage is that in some cases there is more work involved. You need to either draw or scan in everything you want to show the players. You can't just yank the sheet from the folder and place it in front of them. Dwayne, the current GM, is very good at scouring the internet for images and maps to use for his games. Just doing a image search via Google will save you loads of time. In addition buying adventure PDFs becomes even more valuable. You can often just copy the image out of a PDF and use it as a JPG.
Plus you need to keep in mind that if you want to use "miniatures" or tokens in VTT parlance you need to keep all at the same scale. So if your man size is 50 pixels by 50 pixels you want to make sure everything else is scaled accordingly. The good news that there are several vendors and free sources that have a large amount of tokens at a consistent scale.
Adding stuff to your VTT is pretty much a matter of dragging and dropping JPGs and other files into the correct files. Once they are there it appears in the list of stuff you can display. Plus the various VTTs have drawing tools you can use. Fantasy Grounds support a adjustable grid that your minatures can snap too. Drawing tool for freehand drawing. And pointers which are good when you want to find what in a circular radius or a cone. In addition pointers are good for drawing lines.
Fantasy Grounds and other VTTS support what is called rulesets. A ruleset generally consists of a character sheet and a combat tracker specific for that RPG. Some rulesets (like d20) are highly automated some are just fill in the blank forms. Fantasy Grounds has about a dozen official and unofficial rulesets. I have used the default D20 ruleset, along with the GURPS and 4e ruleset found at Four Ugly Monsters A partial list is here that you can look at.
Some of the official rulesets come with rulebooks that you can use for references in the VTT. Personally I have a two monitor setup on my home computer. When I am GMing I have references opened in the left monitor and FG running on the right monitor. When I was playing last night it was easy to log stuff in Twitter because of the dual monitors.
Note that dual monitors are great to work with if you use your computer for serious work (even serious hobby work). Most midrange gaming cards ($50 to $100) have dual monitor port making two monitors a snap to setup.
For people playing the older editions I recommend looking at the Castle and Crusades ruleset.
If you have specific questions I will be happy to answer as best as I can in the comment section.