In Dune, it seems to me that the whole theme of precognition makes it difficult for the PCs to have a larger impact on the setting. I played in a Dune one-shot game that was set on a remote system after the original book, where the system was holding out against Emperor Atreides's Jihad - with the option that we wouldn't turn the tide of the jihad, but some negotiation was possible based on unusual stuff going on in the system. As a remote system, it wasn't the focus of the emperor's attention - so we avoided some issues there.
Actually, a major theme of the books is how Precognition is a giant trap, and as a thematic point were an attack on the Great Man theory of History.
If Precognition is a major problem you have two 'serious' options along with a good, if perhaps mildly unsatisfying one.
The Good Options are
A: Play in the time of the Padisha Emperors prior to the events of Dune (as I did in my big creative thread here a couple years ago),
B: Play after the death of Leto II, when a: There are no more major Precogs, and b: the genes to be invisible to Precognition are being propagated throughout humanity (that is, in fact, Leto's Golden Path, through the trap of Precognition, after all)
The better, but perhaps less satisfying option is to play during the events of the first three books but simply don't get involved in Imperial Politics in a major way. Paul and Leto II aren't exactly using their pre-cognition to track down Spice Smugglers or win votes in the Landsraad, you know. Well, maybe a little of the first one, but not ALL Spice Smugglers.
THe key I find with any licensed setting is to simply NOT GET INVOLVED with the events of the books/films/plays/videogames/dream quests of kadath and just use the elements of the setting (other than characters and major events) that actually appeal to people. To take Star Wars as an example, the entire Old Republic phenomenon proves that it isn't so much Luke Skywalker and Death Stars that people enjoy, its far more generic shit like Jawas and Lightsabers and bounty hunters.
In Dune, thats shigawire reels, mentats, weirding ways, prana-bindu techniques and Spice. Toss in some Facedancers, a bit of Semuta perhaps, maybe a foldship or two...
Of course, the Last Unicorn Games Dune seemed entirely playable in the milieu of Noble Houses and their retainers, so what do I know?