I have played games with so-called open choice systems before -- The Witcher, Fallout, etc. Inevitably, regardless of your choices, the game reaches the same conclusion, with small variations. This or that group may by the victors but the defeat of this or that group is always the same.
If the choices you make significantly change the story arc of the entire game... that's rather significant, and, of course, intriguing. But if the game takes 100+ hours to navigate in a single playthrough (a feat easy to accomplish for TES series games), the choices you make don't simply change the course of the game, they change the course of your afternoons for weeks, even months to come, which isn't necessarily a good thing if the results are not playing out as your expected or are pleased with.
Part of any decision system worth its salt in the inclusion of unforseen circumstances. The beggar you shoved aside now returns as ... blank, to seek ... something. I'm not talking Gaenor here, I'm talking about the twist, intrigue, and betrayal from which truly epic tales are woven. I concede that such plot points are almost required for a truly compelling story, but if you know that a simple choice you make in the beginning of the game can come back to really ruin your day (and possibly your enjoyment of the game) days or even weeks later, every turn you take suddenly becomes bittersweet. At some level your disposition towards the game changes as this bit of knowledge hangs in some back corner of your mind while you plod along, questing and looting.
This sort of fine grain, every-action-has-a-consequence (be it logical or unexpected), seems to be what game designers have been pushing for for years (with little success IMO). It's also not really what I'd hope to see unless the ideas is executed to its conclusion, that is to say, having remedies for poor choices (even if they are a pain in the butt), so that unexpected consequences don't ruin what, to the player, might have been a 75 hour investment in time and emotions while they played the game up to that point. Some examples of nicely executed poor-choice-resolution include the alternate Wraithguard activation route in MW, and the vampirism cure quest in OB. These quests were probably some of the most tedious single objectives in their respective games, but they are exactly what I would like to see from any game that introduces a truly comprehensive decision system. Without knowing that you can "patch up" shoddy decision making down the road, the risk/reward balance of taking an experimental route while playing the game will lean dangerously towards the "risk" end of things.
Now all of what I've been taking about has mostly been geared towards MQ type decisions. If you're the person who's tasked with saving the world, it would pretty much svck if your bad decision making really messed up that ends. For side quests and faction questlines, i think it's a little different. Granted, in past TES games there were many side quests where the outcomes were significantly changed depending of your actions, and I liked those. What it would be interesting to see would be the long-lasting, tangible, (and sometimes unexpected) consequences tied to faction questlines. A simple interpretation of this might be the players inability to advance or even join the ranks of a particular faction of they are involved with or are of a certain rank in a different competing faction. The mutual exclusion of the Great Houses in MW was a good example of this. But I think I'd be just fine with having even more unmitigated story ruining choices if they are relegated to particular factions, In fact, I think it would be quite realistic. It would be the equivalent of ruining your career, and what do you do when that happens? you pick up and move on, in this case it would be to pick up and move to a different faction.
All in all I'd much rather see the story-altering decision mechanics applied to side or faction questlines rather than the main story, because I would much rather have my advancement in a particular guild cut short than see a poor decision have sweepingly broad and unrecoverable negative effects for my entire game world.