I have a tenor Bruko tuned EAC#F#. It gives the uke a more mellow tone which I like as well as making playing in certain keys easier. I mix it a bit as to how I approach the chords. Sometimes I think in terms of the "transposed" key and sometimes the sounding key. It depends on circumstances. It's useful to know the transpositions as if you find chords for a song given in a particular key, then you do need to work out what shapes to play for that song.
A usful tip: If the site has a transpose function, then go up a minor third (3 semitones) and you will get the shapes you need to play for that key. I do this with Ultimate Guitar.com as their chords are all guitar based. Here's a little table to give the shapes for common uke keys.
Code:
GCEA key: F C G D A E
EAC#F# key: D A E B C G
So if you want to play in E on an A tuned ukulele, use G shapes. Much easier than in GCEA
Also worth knowing for an A-tuned uke is that capo 3 gives GCEA so if you are playing with folk in standard tuning, just stick a capo on the 3rd fret and you're away. Alternatively, if you know the transpositions, you can just carry on in the tuning you're in. This is when it is worth knowing the transpositions, then you can quickly work out what shape to play.