Page A links to page B
- Is page A about the same subject as page B?
- Is site A about the same subject as site B?
- Are other sites about A also linking to B?
- Is B linking to pages also about A?
- Is link acquisition normal over time or sudden and questionable?
- What percentage of site A's outgoing links appear trustworthy and on topic?
- What percentage of site B's incoming links appear reliable?
- Is site A's or site B's link profile closely related to any known bad neighborhoods?
I don't think you can focus on any one factor, there are a lot of them at play and the majority of sites fall mostly within the normal range. Spotting questionable sites is what Google does, it amazes me how many people think they can sneak links in and not eventually pay for it.