Ashford Castle and Dromoland Castle are both incredible. Ashford Castle was named one in the Top 5 hotels in the world by Travel & Leisure magazine last year, and is on the Conde Nast Gold List. Dromoland, while a bit smaller, is also first class in every way. Stayed at both a few years ago, and would highly recommend both. Each is different...take a look at their web sites. Ashford was the home of the Guiness family. Dromoland has an incredible walled garden.
While we did not stay overnight there (we just stopped in for a cup of tea) Adare Manor is also beautiful
Ashford is in Cong in the Connemera region, while Dromoland is not too terribly far from the Shannon Airport and the Cliffs of Moher. Adare is within an hour of Shannon (I think I correctly recall).
Based on the route you are planning, Dromoland and Adare Manor are probably closer, but if you have time to take in the Connemera region (which is north of Galway), it is lovely. Sky Road is listed in the National Georgraphic Journeys of a Lifetime book, and Ashford Castle can be considered a destination itself. Both castle hotels offer two-night specials that include breakfast and one dinner (email the hotels, if you don't see a special on line).
Enjoy Ireland -- it's a very special, welcoming place.