If you're going to approach someone you're interested in whether they are alone, with a friend or with a group it's best to start with a false time constraint. A false time constraint is something you say first to make it sound like you are only going to talk to them for a moment. Why? They don't know you. They don't know if you're someone they want to talk to. They will be more receptive to you if they think you're only going to stay a second. This buys you some time so you can win them over with your magnetic personality.
 
False time constraints are flexible you can use them anywhere; at a bar/club, at a cafe, on the street, etc.. Say them before anything else you planned on saying.
 
Start with hola, disculpe (excuse me, formal) or disculpa (excuse me, informal), then...
 
Mention that you can't stay long:
 
I've only got a minute...
Solo tengo un minuto...
 
I can only stay a minute...
Me puedo quedar solo un minuto…
 
Quick question...
Una pregunta rápida...
 
I have to go...
Me tengo que ir...
 
And the reason you can't stay long:
 
My friends are waiting for me.
Mis amigos me esperan.
 
I have to get back to my friends.
tengo que regresar con mis amigos.
 
I'm on my way to a business meeting.
Estoy de camino a una reunión de negocios.
 
These are good reasons because they also communicate that you have friends, they like you and you aren't an axe murderer or you're a businessman and important, etc. These are better to say than stuff like "I don't want to miss the bus."
 

You don't need a magic bullet to get a conversation rolling. If you are traveling in a Spanish speaking country one of the most natural ways to open a conversation is to ask for directions or a recomendation. I added a bunch of these basic phrases to the Hook Up Spanish Phrase Guide.

A taste:

Recommendations:

What's there _____ around here?
¿Qué hay de _____ por acá?
¿kEH igh _____ pohr ah-kAH?

What do you recommend _____ around here?
¿Qué recomiendas _____ por aquí?
¿kEH reh-koh-mee-ehn-dahs _____ pohr ah-kEE?

more basic openers here

The literal translation of the above phrases is "Are you accompanied?"

Here's a couple ways to ask if someone is traveling alone or with others:

A couple responses to any of the above:

I’m by myself.
Estoy solo/a. (o= for males, a= for females)
ehs-toy soh-loh/ah.

Here are a few openers you can use in ANY bar or club in a Spanish speaking country. These are casual conversation starters you can use to get some small talk going. They work well for someone you are attracted to or if you just want to hang out with some locals.

What's the best national beer from this country?
¿Cual es la mejor cerveza nacional de este país?
¿kwahl ehs lah meh-hohr sehr-veh-sah nah-see-oh-nahl deh ehs-teh pah-EEs?

What are the local drinks from this country?
¿Cuales son los tragos nativos de este país?
¿kwah-lehs sohn lohs trah-gohs nah-tee-vohs deh ehs-teh pah-EEs?

What kind of drinks are popular here?
¿Qué tipo de tragos son populares aquí?
¿kEH tee-poh deh trah-gohs sohn poh-poo-lah-rehs ah-kEE?

These are good ways to start a conversation since you're showing interest in their country and what makes it different from others. Most people enjoy talking about things that are unique from their country.

Though these are ideal for bars and clubs you can use them anywhere to strike up a conversation.

To get the most out of your time spent traveling in other countries you want to mix with the locals. If you've met some cool people or have met someone you're attracted to and want to hang out with them you can ask them to get a drink with you:

Let's have a drink.
Vamos a tomar un trago.
vah-mohs ah toh-mahr oo-n trah-goh.

If you have any tips or something to add related to this post just mention it below.