2002 Sienna LE 3.0 V6 - 258K Miles - P0304 Cylinder 4 Misfire with MIL...Occasional Flashing MIL

Scotty, My '02 Sienna with 258K miles has seemingly suddenly developed a very noticeable misfire.  Some history:

- In the last 30K miles, occasionally throws P0330 - Bank 1 Knock Sensor with MIL, even after replacing the Knock Sensors and harness

- P0420 Catalyst Efficiency Low once the Cat flag is ready with MIL

- P0500 Vehicle Speed Sensor occasionally appears with MIL along with no reading from speedometer (ABS, Brake Light will occasionally illuminate).  Speedometer also will sometimes read speeds in an unsteady manner, much higher than what the vehicle is traveling, but the ECM, per my rudimentary scan tool, believes that the vehicle is going at the expected, not indicated, speed. VSS replaced to no avail.

- Drove 700 highway miles this past weekend with Chevron Techron Fuel System Cleaner added to the first tank of the trip.  Upon arrival from the trip, after the next filling, the engine began to run rough.

P0304 (Cylinder in Bank 2) will set and rough running occurs regardless of RPM or load.  With scan tool, I have found that the long term fuel trim is acting strangely with Bank 2 about 15 higher than Bank 1.  Starting is not hard. No hesitation, but power is definitely reduced.

At Idle - 825 rpm - SHRTFT1 -0.8, LONGFT1 -12.5, SFRTFT2 0.8, LONGFT2 4.7

At 3100 rpm - SFRTFT1 -2.3, LONGFT1 - 0.0, SFRTFT2 - 0.0, LONGFT2 14.1

Prior to all of this starting, Bank 1 LONGFT would hover around 0.0 +/- 2 regardless of RPM or load, and Bank 2 LONGFT would hover around 9.0 +/- 2.

I have absolutely no idea where to start looking to figure this out.  I don't want to just start throwing parts at the problem as our funds are pretty low in this current economy.  My initial thoughts are a vacuum problem in Bank 2, but that doesn't explain to me why the LongFT drops to 4.7 at idle.  I can't imagine it being a MAF since I would expect to see the fairly lean reading across both banks, not just Bank 2.  I have thought that perhaps either the Bank 2 Cat has expired/clogged, or the Bank 2 A/F sensor is faulty, but Cyls 2 and 6 aren't reporting any issue.  Could it be electrical, such as a Cyl 4 coil pack or the plug?  Fuel delivery such as a faulty fuel injector at Cyl 4?  I have included the P0500 and P0330 history but I cannot see how they would correlate to a Bank 2, Cyl 4.  Unfortunately, my scan tool doesn't provide misfire counts.

Any ideas to help narrow this down would be greatly appreciated!  Thank you!

TexasTea