carsnocean - the drive from EWR to ITH is 4.5 to 5 hours, factor in one stop for bathroom, food/snacks/coffee & fuel - "Waze" your way toward I-80 West, I-380W then I-81N, etc. Most urban traffic should be behind you once past Morristown, NJ - depending on day of week & start time from car rental. Drove this route but with our starting point in NYC last month, left at 6:15 AM on a Sunday & traffic was very light - some highway construction on I-81 (an easy drive but not as scenic ... last drove this 20 years ago, LOL) ... on this popular trucker's route - vehicles moving above the posted speed limit mostly, 70 mph in a few stretches in PA.

On summer weekends, not unusual for parents with teens making pilgrimage trip to see universities and checkout campus & off-campus housing, etc. or even start hauling trailers worth of furnishing on the highway, no matter which way you decided to fly into & aim for the colleges dotted all over the NY landscape. With the limited inventory of hotel rooms, especially on weekends - if you find something, book now & lock it up first while you hunt for a better/free deal.

Otherwise, BUF might be worth considering, especially if your points can be used to book a nonstop - drive is about 3 to 3.5 hours, shorter than EWR for sure but on tolled NYS Thruway, traffic will be buzzing along around 70 mph (just stay with the "pack" to avoid getting singled out & pulled over by the flashing red.) A long, boring drive - especially if you are tired & not fully rested ... on our return trip last month, took us far longer than planned with the ladies in the minivan taking too many restroom stops :D in a light rain.

Cornell commencement is the Sunday of Memorial Day weekend. If the OP will be flying in that Friday or Saturday, then the drive from Newark to Ithaca could be nightmarish. I wouldn't do it.

Also, we don't yet know whether the OP plans to go directly to Ithaca upon landing somewhere, or if he plans to check into his SYR hotel first.

I did 40K mileage run earlier this year consisting only of long-haul/ultra long-haul and making sure all my SWU's clear. I found that planning a lot less stressful! Didn't realize weekend trip to upstate NY is gonna be such a PITA. If it wasn't a family member's ceremony, I would have mailed a Amazon GC with a congratulatory note and be done!

Now... OP would prefer going to SYR for hotel. However, it all depends on arrival time. I don't have WN's flight schedules yet so it's tough to say. Acc to current schedules, WN inbound at BUF is at quite an unreasonable hour. Also, planning on flying after work week so the sucker (i.e., me) is going to face brunt of traffic in every way. And, might I add, commencement being on Memorial day doesn't help things at all!!

Car rental from BUF, ROC, SYR is quite affordable. It feels BUF/ROC/ALB/SYR are best choices from ORD/MDW. Most likely, BUF given WN flies there and has unrestricted award inventory. Any thoughts on that specific driving route? I doubt AA is going to lower prices for SYR or open award inventory.

WN typically had 3 nonstop flights between MDW & BUF leaving at 9:00, 13:30 & 22:20 arriving ~2h30 minutes (90 min flight+1 hour time change). If you were to leave after work on Friday you can grab a relatively inexpensive hotel near the airport (there are man) and then drive the nice 3 hour drive to Ithaca the next day. I know you said you had a hotel in SYR but you might be able to find something closer to Ithaca.

"Most likely, BUF given WN flies there and has unrestricted award inventory. Any thoughts on that specific driving route?"

AA and UA also have unrestricted award inventory; it's just a question of how many miles you are willing to pay. WN's award seats are priced based on the available cash price, so a WN award seat will not necessarily be a bargain, but might still cost fewer miles than an AA or UA unrestricted award to SYR.

Once you figure out where you are flying into, and whether you will be driving directly to Ithaca or going to your hotel first, let us know, and we can better advise you re: driving directions. But what you'll find on MapQuest is likely to be what you should go with.

Any suggestions on something Marriott/SPG/Hyatt?

exactly what you said

Downtown Buffalo, about 15-20 minutes away from the airport, has all 3 including a rather new Westin and quite a few new Marriott properties. At the airport there are a few Marriott properties and an Aloft property. Car rentals rates may be even cheaper at the locations across the street from the airport next to many airport hotels.

As for nearer to Ithaca you should look at Marriott properties within 30 miles.