The obvious advantage of the Old Town area are that you are right on top of all the sites. The disadvantages are correspondingly high prices and the fact that you are constantly surrounded by other tourists.
Transport into the centre from Andel is very good, with both a metro station and several trams. Walking you can easily get to the end of Charles Bridge in 15 minutes from Andel Metro, or the metro itself takes about 5 to the bottom of Wencelas Square. Andel also has a good number of neighbourhood bars and restaurants.
It isn't, though, the most scenic of areas. The centre of Andel is a big bus station (useful if you fancy a day trip south) and a big mall. (Some people may regard this as an advantage,I'm not so sure!)
I always stay out of the centre. Cheaper prices, more sense of Czech life, and transport is so good that you can be in the centre in minutes anyway.
As always though it's a matter of choice.
Cheers
Alan