Not sure I understand the question, but here goes:

I. Short Answer
NJ Transit from Newark Penn Station to NY Penn Station. Fastest (assuming your travel time to Newark Airport Rail Station and Newark Penn Station are comparable) and most frequent service. But costs more than PATH, if that matters.

II. Longer Answer
First, this is a pretty good summary: https://new.mta.info/guides/airports/newark-ewr#

The transit options from Newark Airport are:
- bus
- NJ Transit rail

The transit options from Newark Penn Station are:
- bus
- NJ Transit rail
- PATH (“subway”)

BUS
You’ve ruled this out, which IMHO makes a lot of sense.

PATH
The PATH train that runs to Newark Penn Station goes to the World Trade Center, not midtown. To get to 33rd Street in Manhattan you will need to change trains. You can see the map and schedule here: https://www.panynj.gov/path/en/schedules-maps.html. I consider the PATH inferior to NJ Transit if you’re trying to get to midtown, but it’s cheaper.

NJ Transit
All NJ Transit trains that go to/from Newark Airport also stop at Newark Penn Station. And there are additional NJ Transit trains that go to/from Newark Penn Station that do not stop at Newark Airport. You can look up train schedules here: https://www.njtransit.com/train-to

Assuming cost is not an issue, I would check on the transfer time from your hotel to the Newark Airport Rail Station and to Newark Penn Station. Determine the total travel time and choose accordingly.

Grand Central
There is no public transit directly from New Jersey to Grand Central. You would need to get from NY Penn Station or the PATH to Grand Central by an additional form of transit.

I hope this helps.