In my opinion there is such thing as a minimum R^2 value for any analysis of any design. R^2 is but one number that helps articulate the variability accounted for by a specific model. The goal of your analysis is not to get 'good statistics'...but satisfy your experimental goals and objectives. So if those goals and objectives are not answered/satisfied...I couldn't care less about R^2 and any other statistic. With regard to the other three questions you pose 'how do I find these'...those are addressed by domain knowledge, experimental conduct, past experience, and any first principles knowledge you can bring to the problem at hand. So let me start and try to help.
1. Wrt to levels, if you are in a position where you truly do not know where to set levels, then DOE is probably premature. I hate to recommend it...but if you have no idea, perhaps it's time for one factor at a time trials to see if you can find those levels.
2. Lurking factors...here is where domain knowledge plays a big role. For example, maybe you have to run the experiment in two different 'machines'...that you hope are the same...but want to guard against the situation where they aren't identical with respect to how they influence the responses. Here's where some form of blocking comes into play. Or factors are hard to change...like maybe temperature in a vessel so you'd like to restrict randomization on temperature running all the low values together, followed by the high values. In this situation what's called a 'split plot' design (just one form of blocking) is recommended. Think about the experiment and the conditions surrounding it and use your domain knowledge to guard against or at least account for these lurking factors. Also I always tried to be present whenever the experiment was being conducted to just 'watch' for anything that might be suspicious.
3. Way back when you were planning the experiment did you spend some time brainstorming ALL the factors that might be influential? Hopefully, 'yes', and you made a list. And kept that list. Maybe it's time after analysis to revisit that list and try some other factors?
4. As for measurement system variation, the rule of thumb we often used was measurement system variation was desired to be 1/4 the variation of the signal variation we were trying to find. Your situation might be completely different.
Hope this helps?