With only 2 days available to make the most of a city, you’ll want to maximise the time you have by scheduling the best time of day to travel. My general rule of thumb for selecting a destination for a weekend is that it has to be within 2 hour travel time from London (either by air or rail). This way travel time is reduced and you can still hit the ground running and start checking things out.
There are good and bad points to getting in the night before (Friday night if you’re spending the weekend) or first thing in the morning (Saturday morning).
Getting straight out of work on a Friday afternoon and hightailing it to the airport/St Pancras Station is a good idea, if you can score an early flight/train (no later than 19:30 ideally). Anything later than this and it means you’ll touch down at your destination at 22:00 at the earliest, leaving not much time to get your bearings, find the hostel and check in before it’s almost midnight and you pretty much want to go to bed. The only exception to this is if you find a really fun hostel and meet some people and head out to a bar or pub straight after checking in (this happened in Brussels for me, which was heaps of fun). If this doesn’t happen though, you’re pretty much just paying for an extra night in a hostel with no real other value except being able to wake up first thing the next morning to get out into the city.
Alternatively, you can book a flight/train leaving no later than 08:30 on the Saturday morning. This means you’ll get in before midday, and it still gives you most of the Saturday to explore after getting into town and finding your hostel. The early travel time does mean a real early morning start, having to get to the airport/train station approximately an hour before hand, with an hour of travel time on top of that from your home as well. But hey, you’ve got 2 hours in a B737/A320/Eurostar to kill, have a snooze!
My preference is the Saturday morning option for most trips. What works best for you?