On 3UK the skype client provided for the S60 clients actually makes a regular GSM/UMTS *voice* call to a skype gateway on the 3UK network, and from there the call is connected via skype.

When you use a regular skype client the entire end-end connection is over IP, ie GPRS or UMTS or wifi data

As such you could hit issues with port blocking, performance, or charges that you wouldn't get with S60. Having said that I have a 1Gb+ data limit and on 3UK there's pretty much no port blocking in place so as an end user either "just works".