It's a wonderful film. The 'doppelganger paranoia' bit is only part of it, there's also the well drawn characters, a distinctive setting (which satisfies the horror requirement of isolation) and the wonderfully grotesque and imaginative forms the Thing takes when it's out in the open.
The campaign and one shot versions don't have to be that different. For the campaign I would recommend that infected != 'dead+gone with no hope of reprieve'. Have a cure for the infection exist, which isn't present in the film.
Here's what you'll need:
Half a dozen or more colourful NPCs.
An isolated setting. A dungeon could serve the role of both flying saucer and base.
Some really kickass mad ideas for the Thing's many forms.
My suggestion is for the PCs to be guards on an archaeological expedition to distant ruins. Let's say they are in a desert to hide your source a bit. The ruins are vast and ancient, probably pre-human. This is D&D so you can have a few normal fight encounters before the main event starts. In extensive Clark Ashton Smith style tunnels beneath the ruins something ancient and evil lurks. Or rather, it did. It's already escaped. For the campaign version, the cure for the infection can be found somewhere in these tunnels. There was a previous expedition which was lost without trace. The PC's party encounters the last surviving member(s), who have, of course, been infected by the Thing. The first expedition's supplies were lost in an accident or monster attack, the Thing needs those of the 2nd expedition to reach civilisation.
In this setup the Thing will take the shape of ancient extinct creatures, which might be totally unknown to the PCs, when it comes out to fight. They should be damn weird, whatever they are.
When it comes time for the paranoia, one possibility is to Thing-ify one or more PCs without telling the player. You could use a simple DC system or a save for whenever a character is left alone with a Thing dupe. Best to make the roll secretly for the PCs.
