I've played 100+ sessions of D&D using Maptools & Skype, and I'm a computer moron- if I can do it then so can you.
Having said that it takes a good chunk of time and prep to begin with, you need to constantly keep ahead of the players, and if you want the PCs to be able to explore anywhere then you're going to need to be on your toes.
So here goes-
1) Check whatever your using- Maptools and Skype for instance, works for everyone- the worst thing in the world is to do a shed load of work and then one of your PCs can't access it for whatever reason. Solve any system issues now, don't wait till the big day- get all the players connected and test the thing.
2) Decide on a Framework or not- a Framework is a pre-programmed/specified bunch of data (or at least properties) which you need to make the macros on individual tokens work. So when you're playing the Goblin King and you click on his Macro to 'Attack with Haunch of Meat' the data produced- to hit roll, damage et al calls on the creatures properties which are defined by the Framework- like base to hit, strength bonus, level bonus et al.
Personally I built my own framework which I'm happy to share and if time coincide to demo for you- message me. I built my own because I am a computer idiot (I may have mentioned this) and did not understand how to work any of the existing Frameworks- I tried to make them work but had no success, just got lots of errors. As I say this has nothing to do with the frameworks, they're used by 100's if not 1000's of people- I'm an idiot remember.
That said, if I can build a framework, then so can you... actually so could your hamster.
3) Get resources, maps from-
Cartographers Guild
Cartographers' Guild - The Front Page
Dundjinni
Dundjinni Mapping Software - Forums
ENWorld
See Forums for Maps & Art
RPTools forums
RPTools.net • Index page
And lots of other places- ask around if you're not sure.
Also many of the above, including dundjinni, have lots of object packs (all the stuff you need to build and enhance maps)
Remember you're also looking for tokens, or things to make into tokens- see all of the above but invaluable is RPTools Tokentools- download this as well and get using it.
There's a torrent floating around called 'Maptools', not many sharers but attached to it (I believe) is about 2 gig of maps and objects- that would be almost everything you need...
4) Go back to RPTools and find the tutorials section, have a play through it-0 and practice what they preach, it's a steep learning curve (well, for me it was) but after about four or five days of trying... well, I love maptools, it saved my life once (no, really- no D&D for 4 years and then I bumped into Maptools).
5) Play with the system as much as you can, make notes as you go along- if you need to. Message me here if you need help, or a session in how to do things, although remember I'm on GMT.
To conclude- Maptools & Skype games can be slow (in comparison with face-to-face) you need to learn how to manage the system. It's hard to play without a significant amount of prep- however this can be done between games. It can be difficult to do things on the fly- you need to build up a stock of maps and creatures particularly if you just want to run encounters on the fly. VTTs work best when the players have lots of visuals so its not just maps- art work is good.
Lastly, start with something easy, a pre-packaged scenario would be good- something which you can use as a structure, and provide you with all of the maps, artwork etc.
Do it well and at times its better than the real thing, it does however take time and patience to get really good at.
Cheers Goonalan