Fresno - Never been need suggestions.
Well, due that this is only a food related site you might want to try another website for overnight accomodations.
That being said, depending on the area you are staying in and have transportation, I can reccomend varies parts of town that have great chow and nightlife - if that is the combination you are seeking.
The first being my favorite - Fresno's Tower District. Located (mainly) on Olive Ave, east of Palm Ave and ends near Van Ness. Within walking distance are many wonderful restaurants and bars. On weekends many have entertainment (DJ's, various bands) and typically there is a small to no cover charge. Veni Vedi Veci's has a very happening night scene and always has no cover charge and a DJ - beware, the lines can get pretty long later into the night. I prefer to begin my night with dinner and drinks at Palomino's - the patio is gorgeous, and the seafood specials they have on the weekends are amazing. Other restaurants/bars are Livingstone's, Rousseau, Landmark, Bobby Salazar's, The Million Elephant, Thaiphoon, Sequoia Brewery, Club Fred's and so on...
There is also the Fig Garden area at Palm and Shaw. Restaurants/bars include The Elbow Room, The Chef's Table, Pangea, Belana, The Limelite, Patio Cafe, and Tau. Some have nightly DJ's or music, but you will have to call for more info.
Lastly is the NW Palm area (located at Palm and Nees). Roe, Twist and The Daily Grill have a nightlife and late-night happy hours. Roe just featured flair bartending the other night (if that is your type of thing, I prefer for them to just pour me a drink!!).
Good luck!! Hopefully this helps...
What cocktailqueen said about accomodations. Fresno doesn't really have any high end or boutique hotels, so let price, amenities and location be your guide. Nees, Shaw, Herndon, and Ashlan are the main E > W streets through most of town.
N > S tends to be by freeway: The 99, the 41, the 168. However, Palm is a main N > S between the 41 and the 99. (Be aware the 99 is in BF Egypt--far to the west of most of Fresno.)
If you're in N Fresno or NW Fresno/Clovis, some places I recommend strongly are Bistro Rustico on Palm and Bullard for outstanding Italian, and then Trelio and Cracked Pepper Bistro for creative casual fine dining. Excellent service and food at all three and IMHO Trelio has the best food of that type in Fresno/Clovis.
If you want Asian, I recommend Hunan Restaurant for Chinese and Thai Royal Orchid for Thai. Hunan's food is excellent and TRO's can sometimes be indifferent, but Fresno 'hounds consider it the best Thai in town. I have had excellent meals there as well as more pedestrian ones, so it all depends.
Thai Royal Orchid, 6735 N 1st St, (559) 431-0132
For Mexican, hmmmm. Fresno has tons of Mexican places, but the majority tends to the same menu: Americanized Mexican dishes we all grew up with. I've never been to Cuca's in the Tower District, but it's been reviewed favorably here. IIRC they have more of a non-standard menu.
Cuca's, 936 E Olive Ave, (559) 237-0111
NW Fresno/Clovis doesn't really have much of a club scene unless you like beer joints. If you want to go clubbing, the Tower District is definitely your goal. Follow CQ's advice.
Gotta say the picon is an acquired taste, one that still eludes me.
The food is hearty and simple home-cooked, this is the stuff your mom made: A bland potato salad, chicken noodle soup (ours tasted canned), store-bought bread, an unremarkable beef stew, and then your entree served to you.
This is where the Basque Hotel shines, AFAIC, when you order the garlic fried chicken. Half a chicken, liberally coated in garlic and batter, deep-fried, served whole, IIRC. Mine was juicy, tender and packed with garlic flavor, never too much or too hot. Perfect!
Last time I was there I had the steak, and it was a poor cut of meat: Gristly and not much flavor. I recommend the chicken every time.
Hubby and I enjoy going to Max's. The food is very good, I especially enjoy the seafood preparations there. They have a nice wine list and an inventive cocktail list with nice vodka infusions. I am not quite sure if it is a "happening" place with lots of singles, etc. They do have a bar, but it is pretty small, maybe 4 stools. So, great for dinner, but I don't know about mingling. I do think they might have a happy hour, though, that could be worth checking out.