Friends of mine, a couple, are coming to Tokyo. He will attend a convention at the Tokyo Big Site and she wants to do shopping, which probably will be in the Harajuku-Omotesando area. They're asking for hotel recommendations convenient for these two destinations. I assume they'd want something located in between. Cost isn't really an issue for them, they should be able to afford a nice place. Do you have any suggestions? Thanks.

Le Meridien Grand Pacific Tokyo is close to Tokyo Big Site and overlooks Tokyo Bay. It is quite convenient to get to central tokyo so this may be an option.
There are 2 Le Meridiens (both with the same name, one with Grand) one by Shinagawa so when booking, they should make sure they've booked at the "Grand" in Daiba, Minato-ku.
The Big Site is on reclaimed Odaiba, connected to the mainland by Urikagome line, terminating at Shimbashi. From there you take subway Ginza line for Omotesando, or JR Yamanote line to Harajuku. So bearing in mind the need to have easy access to the exhibition hall, they can be based somewhere near Shimbashi and Shiodome, which boast many good hotels. Top-of-the-range is the newish Conrad Tokyo (from around 50k a double), with Gordon Ramsay restaurant, and a pair of boutique hotels - Royal Park Shiodome Tower and Park Hotel Tokyo (both around 27k a night).

There's also the Tokyo bay Intercontinental (which may not be such a deal as it often shows up on Priceline).