[ Spoiler ]
Like any fully-fleshed out published shadowrun, On the Run has its problems and requires tweaking to fit a particular group of runners. For me, it involved tweaking the opposition up since I mandated 500 CP characters to start the game. These sorts of modifications are easy for a GM with some experience and, to give the authors credit, the "GM hint" sections of On the Run give good guidance on how to tweak the difficulty of both combat and non-combat encounters.
These minor tweaks aside, I couldn't think of a way of fixing the inherent weakness of the plot. That is, the characters are hired to retrieve stolen property in the form of an old obsolete data disc. The plot relies entirely upon the group deciding, once they've acquired the disc, to ignore their contract and spend time and resources to investigate the origins of the disc by working through several not terribly fruitful legwork encounters. This weakness was discussed in the RPG.net review (and comment thread), if you're interested in more explanation.
I decided to just wait and see what my group would do. Sure enough, when it got to the point that they discovered the disc had "unbreakable encryption" they promptly lost interest and two of the players made strong cases for simply fulfilling their contract and demanding more money from their Johnson on the basis of having been lied to about the status of the object as stolen and for misleading them about the expected threat of the job, i.e. the Shangri-La strike team. They got a bit more money out of the Johnson and handed over the disc.
I awarded Karma and let the group have a few days of downtime. The hacker said that he was going to keep an eye out for rumors on the Matrix over the next week to find out if anything happened to their Mr. Johnson, whose real identity they had uncovered. After a few days I let the hacker know that there were rumors that their Johnson had disappeared. Then I had a powerful Spirit of Man approach the team magician with an offer of employment on behalf of its summoner. The spirit offered the team a job retrieving, you guessed it, the same chip they'd just retrieved. After questions and negotiation the team took the job. A spirit with the Search ability was used to find the corpse of their former Mr. Johnson weighted down on the bottom of Lake Union. I also let them trace one of the email replies the original seller as coming from Ari Tarkasian.
That's where we stopped at the end of last session. Here are my thoughts going forward. I've decided that their new employer is Jet Black* and that Ari Tarkasian's shadowrunner team killed Darius St. George and took the disc. Tarkasian doesn't have the encryption key either and therefore must go through the same legwork the characters were intended to do in order to try to acquire the key. This presents opportunities for the team to encounter agents of Tarkasian. Basically I'm intending that the team eventually figure out where Tarkasian is keeping the disc and make a grab for it. Since Tarkasian is running this job outside of normal corporate channels, I'm expecting the showdown to be with Tarkasian's hired shadowrunner team in some non-corporate location. Should be a pretty tough fight.
Initial feedback from my players indicates they think it's cool to be hired to go after the object they were just paid for handing over. YMMV, of course. I hope this is helpful as a jumping off point for ideas for other GMs, should they encounter similar problems with this story.
*As an aside, I decided that Jet Black is a powerful Free Spirit instead of a vampire. Summoned after his death by a ritual group of obsessive fans with more enthusiasm than skill, he broke free and has spent the last couple decades much as the canon JB has. I made this change because I've run WoD Vampire games with this group in the past and, frankly, we're sick of vampires.
