1024x768 is basically your lowest "safe" setting if you're looking at normal laptop+desktop support and/or Flash support. I'm writing on a 1366*768 laptop display right now and all my screens right now are widescreen, though, so if you were to support a widescreen resolution on native that'd be the one (actually, 1360x768 just to be safe). I really haven't seen many 16:9 screens out there that don't get that high other than netbook ones.
I agree with you, though, it's not a small matter. I'd definitely put some polish in making it run well in smaller monitors while still finding a way to make it comfortably playable on bigger stuff. But when it comes to how big you make your assets... well, that's a huge deal that will determine how expensive and time consuming everything you do is, so pick a scope and go for it. If you let the Internet decide that you'll bleed money trying to make your game look like this:
When, realistically, maybe you'd be wanting that: