I think one of the bigger problems with the Bills in TO series has been the teams they've played. They haven't really had what you'd call a marquee opponent in any of the games played at the SkyDome. Miami, New York Jets, Chicago, Washington and Seattle are not exactly what you'd call great opponents. The two highest-profile teams the Bills have played were both preseason opponents (Pittsburgh in 2008, Indianapolis in 2010). If those games were regular season ones, I'd think tickets sales would have been better. There are a lot of Steeler fans everywhere and Peyton Manning would have moved the needle enough to get a casual fan to maybe plunk down the dollars to see him. If they played the Patriots or the Cowboys, I think you'd see a higher number of tickets sold as well. But no one is going to pay good money to watch the Redskins or the Seahawks.
Another problem is, the Bills just stink. If the Bills were a good team, then people would be more excited about them and would pay to see them. It's no different than the Jays or Raptors. When those teams are good, people head to the games. Toronto just isn't a good sports town. They like the Leafs and that's about it.
The Bills being out of the playoffs and playing second- and third-tier opponents are two of the main reasons this whole Bills in Toronto series has been a bust (and anyone saying it hasn't been a bust is delusional).