Cross the Golden Horn estuary from the old city of Istanbul and you'll find yourself in the district of Beyoglu. Because of social epicenters like Taksim Square and Istiklal Street, this collection of neighborhoods is quite possibly the most lively area for tourists and locals alike, and has been so since it was known in the 19th century as Pera. Which is to say that if you're looking for reliable nightlife and dining intermingled with an assortment of religious landmarks that reinforce the city's tolerant attitude (mosques, cathedrals, and even synagogues), then you need look no further.
Because we go in-depth on Istiklal Avenue here, we'll focus on a few areas less likely to be swarmed with out-of-towners; or at least more popular with Turks. Just west of Istiklal's starting point (near Tünel) is an artsy alternative known as Asmalimescit. This is where you'll catch some of Istanbul's stellar live music at Babylon, 1.5 fluid ounces of pretty much anything at the Asmalı Shot House, and the central meeting place for both good food and tunes, Küçük. Also, keep the fun here if you're into rooftop bars (Balkon Bar is a fixture) or an opportunity to sit outdoors on a warm night.
Another part of Beyoglu worth seeking out is its Bosphorus-side neighborhood, Tophane. If you're an art lover, take a gander at Istanbul Modern and then take your curiosity to any of the dozen or so nearby nargile cafes. This is basically where to go if you want to share a hookah and sip some tea in a lively social environment. There are also a handful of classic Turkish restaurants and non-hookah cafes in the vicinity.
Other nightlife establishments are spread throughout Beyoglu. Some highlights include Nupera, which brings sophistication to a level that matches the superlative view over the water; Jolly Joker, where they truly bring the rock; Hypnos, which serves up the quality DJ's and dancing you'd expect from a city like Istanbul; and the Munzur Cafe Bar, a small, laid-back place where you can catch excellent interpretations traditional Turkish music on instruments like the stringed baglama or the woodwind sipsi.
You'll also get your fix of Turkish coffee or drinks like the yogurt-based ayran in innumerable cafes in the previously mentioned areas or even in the less crowded and inexpensive Cihangir neighborhood. The only advice we'd give as far as finding a restaurant in a district as popular as Beyoglu is to get a little off-the-beaten-path; take an offshoot from Istiklal, head to the unassuming Akarsu Street in Cihangir or check out the potpourri of places near the Galata Tower.
When it comes to Beyoglu, we could go on and on and quite possibly on some more. Just take the metro to the Taksim or Şişhane stations and make Istanbul's world of nightlife and cuisine your oyster.