JFK to Manhattan via AirTrain/LIRR
 

We are taking a red-eye flight to NYC next week and arrive at JFK at 7:45 AM. Looking at the transportation options to get into the city, I think the AirTrain/LIRR to Penn Station seems like the best way given cost of a cab and the amount of rush hour traffic I suspect we'd sit in. The question I have, though, is how packed will the train likely be? Will we be standing for the ride into Penn Sta, and will having a 21" rollaway and a carry-on be a problem?

7:45 AM is part of the rush hour. I would say LIRR trains would be full enough that you may or may not get a seat. But then again there are quite a number of trains going to NY Penn at that time so there is always a good chance.

The trip on LIRR from Jamaica to NY Penn takes about 35 minutes (subject to passenger/train traffic issues and whatever Amtrak might be doing (it is their tunnel between Queens and Manhattan).

I've done it - arriving in the early morning as you are. The train was pretty packed. We had to stand as seats were full. I had a large backpack and it was a bit hard to maneuver. But we did save a bit of money by forgoing the taxi ride.

Or you could take the longer route and hop on the E train - there's a connection from the airtrain to the E train at the same Sutphin Blvd/Jamaica station Airtrain terminus where you catch the LIRR. The E train will be one stop from the start of its route so it won't be full of passengers who alighted on the far ends of Long Island.

A second positive reason to take the E train is that its stop at 34th and 8th (which connects to the west side of Penn Station) won't be as bad a mad house as the LIRR terminal inside of Penn Station.

The negative is the E train will take about 40 minutes or more to go the 14 stops from Sutphin to Penn Station - there are three long stretches on that route: the two express patches and the subterranean crossing of the East River (which you'd have on the LIRR).

It's going to be busy either way, but one thing you might consider is taking a deep breath upon landing, having some coffee, and taking the train after 9 am, when it is likely to be much less busy. If you are checking your 21-inch bag, then you probably won't have it in hand much before 8:30 even in the best circumstances.

What you don't say is your ultimate destination in Manhattan. If it's near Penn Station, then the Airtrain to the LIRR is your best option even if you have to stand, but if you are staying in a different part of town, I might recommend a very different option.

We're staying at the Hampton Inn in Chelsea, so I figured we'd just walk from Penn Station. Still not quite sure whether to take the subway (E train?) or the LIRR.

If you have to stand, the LIRR ride is closer to 20-25 minutes, depending on how many stop there are.

Doug makes a good suggestion. I have landed in London at that time several times. I eat breakfast and then take the tube into town after rush hour has eased up. I am sure the same thing will work in NYC. I always take the metro in from JFK but I arrive later.

The Hampton In is at 108 W 24th St (W24th St off 6th Av) so even if you took the LIRR to Penn Station (W33rd between 7th & 8th Avs) you'd still have to either use the subway or a taxi or walk to W24th St & 6th Av.

If you take the E, transfer at Roosevelt Av for the F (same platform) and take the F to 23rd St (6th Av).

If it's the Hampton Inn on 24th Street, you'd take the E train 1 stop south (toward the World Trade Center) to 23rd Street and walk from 8th to 6th Aves. or walk to 6th Ave from Penn Station and take the F. Either way you have to walk if you are arriving at Penn Station on the LIRR, so you might as well walk from Chelsea, where it's less congested. Or for not much more than the price of two subway fares, you could take a taxi. That's likely to be less than $10, including tip.

But if you are taking the subway (adding at least 30 minutes onto your trip over the LIRR), you can do the transfer, as @nycguy10002 suggests.