Down to the side, or slightly out (not quite a 45) is my preference. I base my opinion heavily on these two things:
1) If you want your model to look even slightly respectable you have to accept the fact that you are going to have to weight it; in some areas, point by point. Life sucks, but it's a good paycheck.
2) Favor where the model is going to be MOST of the time. Usually, even in action-adventure video games, the most active of any work you'll do, the arms still stay pretty much at the sides a lot more than they spread-eagle.
You're going to have issues with any decent shoulders and extra rigging of some form or another no matter where or how you build them, it's a matter of choosing the effort you put in. Do you want to rig it up in the less frequent pose, or rig it into the common ones. If you build your character arms-out you can easily run into "posing" and bone placement problems. Most people, even pros, tend to make the model look good from that raised position taking into account (at least artistically) that your shoulders are up, but then not adapting the bones to that fact (when you, as a normal person raise your arms to the side, you are also raising your shoulders, although this is rarely considered in bone placement, and as a result when the arms are dropped they A) look like the shoulders are "shrugged" and
the arms are too short )
Arms down or very slightly out to the sides overcome the artistic issues best, as you are building what the audience sees most instead of building, (for example) a screaming face that is going to be viewed in a calm pose most of the time. By being where you'll be most, you're "closer to zero".
Back to point 1), the trying to avoid work, or accepting it; technically, to many people, having the arms dropped seems like it makes the weighting harder which is not really true. When weighting, just animate the arms to the sides to get into the tight spots. Easy stuff.
My three cents.