My college roommates and I are looking for a summer long weekend getaway. We are considering the Hudson River Valley - specifically Hudson. We enjoy nature, wineries, shopping, good food, perhaps a spa retreat, and a relaxing scenic location for hanging out. Some nightlife would be nice, but we could also probably create our own fun after having a nice dinner. Is there a better location within the Hudson River Valley? I saw a few nice VRBO in Hudson. Suggestions for an itinerary?

We spent a week along the Hudson River, but most of our interests are different from yours.
For food, how about the CIA in Hyde Park?
For nature, Bear Mountain, Katerskill Falls, Mohonk Preserve.

Try to visit West Point if at all possible.

Also look into the historical houses:

FDR's Hyde Park

Rockefeller estate

Several others - depending on your intrests

Four sites that should be at the top of your list:

*Kykuit (the Rockefeller mansion)]

*Storm King (a magnificent 600-acre sculpture garden)

*FDR's home and museum

*Innisfree Gardens

Do google searches for details.

I didn't mention some of the things we especially liked because they weren't the type of sight you seemed to want, but here they are:
Kykuit
Olana
Walkway Across the Hudson
Storm King
West Point
Manitoga
Vanderbilt Mansion

I've spent a fair amount of time in Hudson over the years, and except for being near Olana and having great "antiques" shopping -- read "mid century modern" -- I don't think it meets many of your criteria.

Thanks to all who have responded. I think after looking things over, staying closer to New Paltz or Rhinebeck might be better options. Walkway over the Hudson, Innisfree Garden,
the Culinary Institute - Hyde Park,Mohonk Mountain House, Minnewaska State Park Preserve, and the Walkill Valley Rail Trail are all possibilities from there. Some of the other sites mentioned look great, but we will probably not want to spend much time on the road.

Any good recommendations for restaurants?

Bicycle rental and popular spots in New Platz area http://www.bicycledepot.com/take-a-r...ew-paltz-rides
Wineries near New Paltz
Adair Vineyard
Robibero Winey
Whitecliff Vineyard ( Gardiner NY, Cafe Mio Cafe in town, very good food)
Shawangunkwinetrail.com
Water Street Market in New Paltz, right next to Wallkill Valley Rail trail http://waterstreetmarket.com/

Minnewaska State Park http://www.nysparks.com/parks/127/details.aspx
Mohonk Mountain House http://www.mohonk.com/ ( beautiful grounds to walk/hike when using day guest pass, relaxing spa)

Millbrook
Innisfree Gardens In Millbrook , love this place (http://www.innisfreegarden.org/visit.html). Beautiful gardens many Adirondack chairs through out to picnic and/or just enjoy the scenery.
Millbrook Winery http://www.millbrookwine.com/index.php

Milton/Marlboro NY
Buttermilk Falls Inn & Spa http://www.buttermilkfallsinn.com/sp...ermilk-spa.htm
Benmarl Winey http://benmarl.com/
Walk way over the Hudson (about 4 miles from buttermilk inn & spa)
https://www.walkway.org/
Not much else going on in Milton/Marlboro area except during apple picking season

Rhinebeck is nice for its cute main street area with shops and restaurants.

Poets Walk in Red Hook (town next to Rhinebeck) and other Hudson Valley Scenic Parks http://www.scenichudson.org/parks/poetswalk

I am not at all sure they will let you on the grounds at Mohonk if you are not staying there,

Being an hour away from Strom King and missing it would be a shame.

My favorite Rhinebeck restaurant is Terrapin.

One can get day passes for Mohonk - but it's paid, not free.

I didn't know that, thanks. That said, I wouldn't bother, personally.

While Mohonk is interesting, I wouldn't put it on the same A list as Kykuit, Storm King, Innisfree Gardens and the FDR museum.

I completely agree.

The Apple Pie restaurant at the CIA (order at the counter, served by student staff) serves really fantastic food (however,the servicer is a little odd - it's possible you'll get your dessert before your main course, and you won't all be served your main courses at the same time, necessarily).

We are not what I would call art or museum aficianados, but we absolutely loved Storm King, and liked the Olana tour a lot. We loved the towns of Rhinebeck and Cold Spring.