Do you want an agent just to book a flight or do you want a tailored trip planned just for you with accommodation, transport, transfers and maybe the occasional guide?
I really liked the Zambian safari sorted out for me when travelling solo. It was efficiently planned, the choices were excellent and they were very easy to work with. They also did it with about 6 weeks lead time when others want 9 months.
Tribes also plans holidays to a wide range of other "exotic" destintaions..
I booked my own flights directly with BA because I wanted a direct flight and there was little choice.
Expert Africa did a good job for a trip to Zanzibar and their suggestions of Chumbe Island and Mafia Island were spot on. However, while they were good, I think they are less comfortable with solo travellers than Tribes, were more expensive and less imaginative, but their size gives them clout to get you in to places that might otherwise be difficult.
For complicated flight plans such as an Around the World ticket, I found Trailfinders excellent, but I don't know if they are in the States. They were always very helpful at finding the best prices and advising routing to do so.For simple flights it is better to go directly to the airline, perhaps having done a bit of research on Expedia as to what is available.
Audley is an agency that specialises in tailored travel (which may be what you are looking for) but I haven't used them myself. They are at the more luxurios end of travel, but have a very good reputation.
The best agency I ever came across for sorting out a solo trip is Inside Japan which has a range of about 2 dozen "self-guided adventures" that are suggested itineraries with different themes and prices which include transport, accommodation , the occasional private guide, a 24/7 emergency number in Japan and lots of information for an amazing trip.
You can adjust the "self-guided adventures" or you can have them construct a tailored trip.
Edited: 4:49 am, January 08, 2013