"I don't get this desire to seek ephemeral causal factors for what was obviously negligent behavior on behalf of the pilots. ... The mistake made by these guys is inexcusable in the extreme."
Nobody here is making excuses for the pilots. They failed miserably in one of their primary duties, verifying the correct runway. The speculation and questions raised are a normal part of trying to determine all of the causal factors, so they can be addressed, corrected if possible, and hopefully avoid similar occurrences. The NTSB will ask the same questions and a lot more, then issue a report. They will recommend changes to rules, regulations, runway design and markings, etc. - if they conclude that such recommendations would be useful in preventing future tragedies.
The answer to your question in your example is YES, if 'other factors' warranted it. To illustrate, let's restate your example and add a few 'other factors'.
Yes, you would be negligent and your mistake would be inexcusable. However, to prevent similar accidents in the future, the other factors must be addressed.
Sound farfetched? Not really. In Texas, we have some state highways that have very wide grassy medians - as wide as 50 yards or more in some spots. Many of these highways do not have over/under passes, but instead, have cross-overs. That is, a side street or FM road crosses the highway which might have a 65 or 70 mph speed limit. Many of these cross-overs do not have stop-lights or even street lights and very limited hard-to-see signs, so at night it is really treacherous to cross or turn onto the highway. Turning left from one of the side streets or FM roads can be especially hazardous at night if the median is wide and traffic is light. You can wind up driving into oncoming traffic very easily. Most accidents at these intersections usually involve strangers unfamiliar with the area, but sometimes even locals mess up. (Many of these highways are being upgraded with better designs, but it's a long, slow process.)
How about all those Texas frontage roads that are two way? Or one-way to the freeway entrance ramp and then change to two way?
No evidence exists to suggest that signs/markings were obscured, or any of the other imaginary conditions you've intro'd into the scenario. The runway was repaved, the taxi instructions might have been different than the last time they were there. So what. You can cite only one incident, 13 years ago, when someone else was confused.
Again, the issue is pilot performance. Taxiways and runways are parts of a system that expects actors to perform as trained and accept some level of performance deviation. The system is not designed to be idiot proof. Such thinking drives up costs, decreases crew awareness and responsibility, etc.
I just spoke with another ATP, just to make sure I'm not crazy. He thinks these guys were probably chatting through taxi, or otherwise distracted, but he still can't figure out how two pilots could make this basic error. He finds it indefensible. He said the error was more egregious and less understandable than the AA pilot that snapped the rudder of the Airbus at JFK in 2001. Only thing he could think of was when two pilots repositioning a CRJ were cowboying around at the edge of the flight envelope and crashed the thing. He thought it happened about 5 years ago.
I honestly think you're abusing failure analysis and systems design practice in your suppositions of cause. Systems are designed to comprehend and mitigate reasonably avoidable risks. Systems can even comprehend reasonably predictable mistakes, but not something like this.