Why not James Marster as Harry? I just picked up some of the audiobooks and his voice is set in my head for Harry then Sarah Michelle Gellar can be Murph (making the size about right for both).
James as Harry was an original concept for the TV show... he just turned it down because he wasn't willing to leave his kids and move in order to film it. (Altogether now: awwwwwww!) I'd love for James to play Harry, but there are several issues that I regretfully have to acknowledge about that, and the first and most prominent is his height. Harry's nearly 7' tall, and James is somewhere around 5'9" to 5'11". And if you were to cast James with Sarah (which would make millions of Spuffy fans hearts gleefully burst in happiness, lemme tell you), the lack of excessive height difference would be very noticeable. Murph's a munchkin compared to Harry.
The books say that Karrin is 5' even -- Sarah is 5'3" which works fine as far as height goes. She's athletic, and she actually has been studying martial arts for years just like Murphy (though her prowess is in Tae Kwon Do, not Aikido), and bonus -- she's done the kick-ass heroine before. The books also say that Murphy's got cheerleader good looks, and hey, what was Sarah for nearly a decade if not a butt-kicking tiny blonde cheerleader?