Old Town or Little Quarter?

both are fine, give me links to both places and I can advise better,I am in Prague several time a year ,back there in April and then again in August,know the place pretty well.
Old town is great and most of the major tourist sites are there, easy to walk into the new town and to other areas.loads of options on Public transport. Mala strana , is good too but there are a lot of places that might be on steeper roads so you might have a bit of a climb to them but you are closer to the Castle area.

More stuff is on Old Town side. Train stations (Main and Masaryk), main bus station Florenc, department stores, shopping malls, Wenceslas Square. Little Quarters or Mala Strana in Czech is also medieval neighborhood, quite hilly, close to the Castle, US Embassy is there, Petrin Orchards, Petrin Tower, Museum of KGB, (Museum of Communism is on Old Town side). If I would be deciding which to choose it would be based on exact location. Certain location in Little Quarters have fantastic views.

Personally I would choose the Little Quarter...it's much quieter than Old Town. You would not be at all far from everything you want to see especially if you make use of the tram system. The city is not large and is very walkable.

We stayed on the edge of the old town at the Green Garland from Rick's book on our 2011 trip. It was a great location, easy walking distance to the main square. Pretty busy in that area though. Our last night in Prague we went to the Little Quarter and I thought, wow what a nice little neighborhood—this could be our place for next time. But we did love the Green Garland and might stay there again next time on that basis. You really can't go wrong either way—things are close enough it's not going to matter for you ability to get to the sights that you want to see.

I much prefer the Little Quarter - much quieter, but walking distance to Old Town, which has massive crowds. Hotel rates may also be lower in the Little Quarter.