I think the whole "Turn-Based doesn't sell" stuff is baloney. I think that a Turn Based game could definitely sell if it was marketed properly. Anyway, according to Leonard Boyarsky, ToEE was by far the biggest seller of the three Troika games and yet it had one of the best and most complex tactical RPG combat systems developed. Of course it was rubbish in the roleplaying department, but still the potential for a Turn Based RPG is there. I've always said that ToEE's combat and engine combined with Arcanum's plot, meaningful choices and non-typical setting would have made an RPG that would have dwarfed even the big shots like Fallout. I'd really like to see a similar Turn-Based RPG developed by Obsidian. Besides, it's not like RTwP games are renowned for their awesome combat (NWN2 was rubbish in this regard.) I think it's an awful design choice personally. Like you said, I'd like to see some more hardcore RPGs developed by Obsidian even if they are lower budget then the AAA titles like Alpha Protocol. Hell, if Stardock -a company that produces 4X million sellers- thinks that a hardcore Ultima-like RPG has the potential to sell decently then I'd trust them on that account.
As for settings, I'd really like to see a Wild West/Weird West cRPG. I know that there are a few PnPs that have covered it but as of yet no cRPG has. It has great potential for a setting. Aside from that, a Steampunk-Fantasy setting like Arcanum or Wizardry 8, a cyberpunk setting, or a hard Sci-Fi rpg (no Space Opera stuff) would be nice.
Obsidian's direction isn't concerning me too much, although I am worried that Alpha Protocol has been compared to Mass Effect more times than it should have. However, I'm still hoping that it will have a Deus Ex, SS2 or VTMB vibe. Regardless, I pray that they won't forget the more hardcore fanbase in their attempts to appease a different audience. Certainly Bethesda have long dumped that section of their audience since Daggerfall and BioWare seem to be going in a similar direction. However, Dragon Age will be an indicator of BioWare's intentions and I'm cautiously optimistic about it. Let's just hope that Obsidian haven't forgotten their core fans and will bring some more grassroots stuff out in the future.