In a spiritual phrase the segment says
...have mercy on me, a sinner.
could you use "upon" rather than "on"?
I feel that using "upon" personalizes the phrase better.
Or is my grammar failing?
"On" and "upon" are interchangeable most of the time. Not always.
He once wrote a book on Shakespeare's sonnets.
Can't use "upon" here.
Upon sounds a notch more formal and can be a lot more emphatic, depending on the context.
There's some wild talk about "upon" only being used where actual physical space is involved, but it doesn't make much sense: "Upon my honor" is a perfectly legitimate phrase.
To confuse matters further, you can (and are encouraged to) use onto where both space and action are involved:
He climbed onto his horse.
Climbing upon one's horse is permissible, but climbing on does sound a bit comical (evoking, as it does, the image of a rider doing some climbing while already sitting on his horse).
"'The Jesus Prayer' (Greek: Η Προσευχή του Ιησού, i prosefchí tou iisoú; Slotho d-Yeshu') or 'The Prayer' (Greek: Η Ευχή, i efchí̱ – literally "The Wish") is a short, formulaic prayer esteemed and advocated especially within Eastern [Orthodox] Churches:
'Lord Jesus Christ, Son of God, have mercy on me, the sinner.'”
As such, I would not advise messing with it to make it more "personalized." But that is just my opinion, and you are free to change it as you please. Good luck!