Human Head Studios' Tim Gerritsen has posted this message on the Rune forums, mentioning that Rune sequel might happen. A lot depends on the success of Prey, but some fan support is needed as well. The forum post also offers a Human Head Studios history timelime. Thanks Blues.
If you really want a Rune 2, though, you need to tell it to the publishers. We want a Rune 2 some day. We've always said that. It is the pubs you need to convince. They see a game with a so so meta critic score and a devoted, but smallish audience and sales that were good but not great. Of course you and we know different. Rune was a major labor of love, and I believe firmly that anyone who actually plays the game for more than an hour can see that (after the water level and all those crabs in caves, of course...) Seriously, though. Make your voices known to the publishers. If we say, 'Rune has a truly fantastic following, even now, five years on' they just look at us like "Sure, five people, right?" If we show them forums, they just shrug. If this wonderful group of hard core, dedicated fans were to all shout at the publishers, however, that speaks volumens. If they know that people are stoked, that Rune really was an overlooked gem, and, most importantly, wallets would open at the sound of Rune II on a shelf, then they would listen.