Guyana's large areas of wilderness, with few roads and few airstrips, mean its little known interior is largely left to nature. There is just one road, mostly unpaved, that serves the length of the country, passing through deep forests and wild savannahs below the rugged mountains of the Guaiana Shield. Flying in a small aircraft, driving by rugged 4WD, or remote river travel are the only ways to get about. With such a simple range of options, the best way to see Guyana is, in practice, almost the only way.
This itinerary, which I have travelled myself, goes deep into the interior, to some fabulously remote and natural places. The travelling is rugged (but not too rugged) and the accommodation can be basic (but not too basic).
If you have more time you can include the 'Macushi Life' side trip, which fits in at Day 5 of this trip, and the 'Kaieteur Falls' add-on, which would come at the end of your stay in this fabulous, little known, and greatly under-appreciated country.