I'll throw my two cents worth in. Also had the iPF 8300 for several years but changed to the Pro 4100 around 4 years ago. Like you having owned many of the Epson's both desktop and large format the thought of going back to those troubles were too daunting for me. I have no regrets regarding the 4100 and thus far knock on wood no issues what so ever. I have not found the new ink set with the 4100 to be worse, not sure where this is coming from. I make all of my own custom printer profiles with X-Rite i1 Profiler 3.
The only thing worth complaining about is the new integrated printer plug in module from Canon. It really does take sometime to get used to it, nowhere near as user friendly as the one with the 8300 but it still beats the crap out of the CMD + Print scenario you would be stuck with on an Epson sans aftermarket RIP.
The 4100 is faster, quieter and produces stunning prints assuming you have an excellent printer profiles. I have yet to see any canned printer profiles from the manufacturers top notch but Canson's are not too bad. Please let me know if you have any questions. Be glad to answer if I can.