Portland to San Fran Roadtrip - Help?

My wife and I are taking a huge road trip down from Vancouver to San Fran. We'll be spending 2 days in Portland and 1 day somewhere in southern Oregon (maybe Medford?)

I really don't have a clue at all about ANYTHING in Portland....

1) Where are the best places to stay or hang out? What streets compromise the downtown area?

2) I want to hit up some breweries but I also want to visit a Williamette vineyard. Suggestions? Is there a consensus of the best 2-3 breweries there?

3) My wife loves sushi and we're in Colorado. So naturally I gotta visit some places there. Any suggestions?

4) Any must-sees in southern oregon?

Thanks in advance if you can help, and if you're ever coming to Denver I'm happy to return the favor

Bamboo Sushi in Portland is a can't miss for sushi while in Portland.
There are so many sites with very complete information on Portland in general, and there are a ton of threads in the Oregon section with peoples' opinions on where to visit for beer.
You'll probably see lots of my replies on the similar threads, but will repeat Cascade Barrel House for sour beers, Hopworks Urban Brewery for a Portland-ethos brewpub with some great beers and pub food, and Laurelwood for some great IPAs along with some solid other styles of beer with a wide variety of good food.
For wineries, near I-5 to avoid a long detour out of the way I'd recommend Willamette Valley right off of I-5 just south of Salem and King Estate outside of Eugene. There are tons of others, but you could spend hours driving around in traffic or lost on small backroads checking them out. Both produce decent Pinot Noirs and Pinot Gris.

So many brewpubs in Portland. One of my favs is Deschutes, but it's a little more "mainstream" than others in the area. Hair of the dog is a good spot, cascade barrel house like mentioned before, rogue is OK, lucky lab is good, Portland U Brew is a spot that a guy does basically homebrew on a barrel system and let's public brew on his system. They have a pub as well. Pyramid is there, widmer bros, mcminimens basically has a spot on every corner (they literally own Portland). Im in Portland several times a week. If you want more info just hit me up

Pro tip: the light rail in Portland is great, and around downtown, free. Stash the car at your hotel and hit an extra brewery or two.

I'll second what others have said about Cascade and Deschutes... Deschutes almost always has a couple limited releases or brewed-on-site experiments, so, they're worth a pint or two, even if you're up to your ears in Mirror Pond and Black Butte; Cascade makes some of the best and most interesting (though, not always both in the same beer... they try some crazy stuff) American sours.

McMinimen's has solid but unremarkable beer, but most of their locations double as hotels, if you're looking for something funky and not on too tight of a budget. I usually end up at the Mark Spencer when I'm in town, also not the cheapest, but very conveniently located to the downtown breweries/pubs, as well as the light rail for the ditch-the-car plan.

On the way down to California, Crater Lake is supposed to be awesome, but possibly closed this time of year? I think you'll find a lot of the beautiful outdoorsy things closed and/or extremely damp.

Hope it's not too late, but here's my 0.02...

1) Depends on who you ask. There's definitely an east side/west side divide (the Willamette river). North Portland is known for gang activity, SE is kinda known for it's drug issues. West side is nice, but kinda removed from all the fun, touristy, fun Portland stuff. Like the other posters said, I'd stay near the MAX tracks in downtown. DO NOT stay on MLK or near it!

If nothing else, Portland definitely has a drinker friendly night vibe going. Hell, they even shut down a few square blocks on the weekends to traffic to drunk people won't get hit by cars while jaywalking...true story. My favorites are Barrel room and if you want the definition of a dive bar...Yamhill Pub (there's a broomstick in the bathroom to be used as a lock).

2) All the Simpsons characters were named after downtown Portland streets...that should give you a clue. Nob hill, Pearl District, and the Waterfront are all must sees. Chinatown is kinda janky. Mills end park (look it up), Pioneer Courthouse Square, Pittock Mansion, Rose garden, Portland underground tour (starts at Hobo's bar) is neat, and all the Portland fountains are way cool.

3) Yuki's in Nob Hill is good and so is Mio Sushi, but I'm not a Portland sushi aficionado.

4) Medford has GROWN! When my wife and I made the same trip to SF, we stayed at the Rouge Regency in their Presidential suite. It was surprisingly affordable and they have a great sports bar with comedy shows on the weekends attached to the hotel.

hope this helped,
HAVE FUN!

Thanks floppy we are about to finalize our plans and this helps a lot! Very much appreciated. If you're ever coming to denver feel free to ask and I can return the favor!

If I was to pick a hotel outside of downtown, which one of these would you pick?

Hard to help because we can't click on the map to see what the hotels are.
Staying in Beaverton (far west side of map) puts you in suburbia and a long way from anything much going on for brewing or touristy/entertainment related. Gresham (far east side of map) isn't a nice place to stay and is far removed from any action.
Clackamas is suburbia but easier access to many SE PDX breweries and is safe, with a big shopping mall, no breweries. Tigard is suburbia and little to no breweriana but has a below average for PDX brewpub, Max's Fanno Creek.
Nearby airport also works with decent safety and access to Portland itself but nothing much going on in the immediate area.
Another option to check out is McMennamin's Kennedy School hotel/brewpub in NE PDX (look it up). McMennamin's is crappy to average on beer but the hotel is neat and close to stuff.

If Its not too late, Stay at the Kennedy school... The place is awesome, but mcmenamims is just ok. You'll have an awesome time, bu it's just out side do the main down town. The thing is there are loads of places in the surrounding area and it's more of an area with the real "Portland scene"

I can tell you my favorite sushi is in Milwaukie. But you will waste half your trip waiting in line.

Read the Portland subreddit /r/portland and do some searches on it. Read the comments, You'll get A LOT of cool info about our town. From a lot of people.

Here are a few random ones, but you can probably search for breweries etc...

http://www.reddit.com/r/Portland/comments/qg4p6/things_to_do_in_portland_the_list/

http://www.reddit.com/r/Portland/comments/qwuqj/if_you_have_only_one_meal_left_in_portland_never/

http://www.reddit.com/r/Portland/comments/o1fen/we_all_know_and_love_portland_but_what_of_the/

http://www.reddit.com/r/Portland/comments/1c4zpr/what_are_some_places_that_make_you_love_portland/